Association between underweight, serum albumin levels, and height loss in the Japanese male population: a retrospective study.

BACKGROUND: Previous study has shown that height loss (defined as the highest quartile of height loss per year) was inversely associated with serum albumin levels. Furthermore, comparatively healthy hyponutrition has been linked with being underweight; as such, underweight might be inversely associated with serum albumin levels and positively associated with height loss. METHODS: To clarify the associations between serum albumin level, underweight status, and height loss, we conducted a retrospective study of 8,096 men over 4.0 years (median). RESULTS: Serum albumin level at baseline was inversely associated with being underweight (body mass index [BMI]: < 18.5 kg/m2) at baseline and height loss. The known cardiovascular risk factor adjusted odds ratio (OR) and 95% confidence interval (CI) of underweight at baseline and of height loss for 1 standard deviation increment of serum albumin (0.28 g/dL) was 0.79 (0.70, 0.90) and 0.84 (0.80, 0.88). Underweight was also shown to be positively associated with height loss: with the reference of normal-low weight (BMI: 18.5-22.9 kg/m2), the adjusted OR (95% CI) was 1.60 (1.21, 2.10). CONCLUSION: Comparative healthy hyponutrition, which is related to low serum albumin levels and being underweight, is a significant risk factor for height loss among Japanese men. These results help to clarify the mechanisms underlying height loss.

Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Association between atherosclerosis and height loss among older individuals.

Atherosclerosis and height loss are each reportedly associated with cardiovascular disease. However, no studies have found an association between atherosclerosis and height loss. A retrospective study of 2435 individuals aged 60-89 years who underwent annual health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. Height loss was defined as being in the highest quintile of height decrease per year, as in our previous studies. Among study participants, 555 were diagnosed as having atherosclerosis. Independent of known cardiovascular risk factors, atherosclerosis was positively associated with height loss. The adjusted odds ratio (OR) was 1.46 (95% confidence interval, 1.15, 1.83). Essentially the same associations were observed for men and women. The adjusted OR (95% CI) was 1.43 (1.01, 2.04) for men and 1.46 (1.07, 1.99) for women. Among older individuals, atherosclerosis is associated with height loss. This result can help clarify the mechanism underlying the association between height loss and cardiovascular disease.

Retirement status after the age of 60 years modifies the association between anger expression and the risk of cardiovascular disease: The Circulatory Risk in Communities Study.

AIM: Anger expression is associated with an increased risk of cardiovascular disease. This positive association was confined to individuals with lower perceived social support and outdoor recreational activity. However, the effects of retirement status remain unclear. This study aimed to investigate whether retirement status after the age of 60 years modifies the association between anger expression and the risk of cardiovascular disease in the Japanese population. METHODS: This longitudinal study included 499 community-dwelling retired and employed workers aged 60-79 years, who completed a cardiovascular risk survey in 1997. A Cox proportional hazards model was used to estimate the hazard ratios and 95% confidence intervals of incident cardiovascular disease (ischemic heart disease and stroke) according to anger expression in retired and employed workers after adjusting for potential cardiovascular risk factors. RESULTS: A total of 37 participants experienced incident cardiovascular disease during the mean follow-up period of 14.8 years (standard deviation 5.5 years). In retired workers, anger expression was associated with an increased cardiovascular disease risk, whereas no such association was observed in employed workers. The respective hazard ratio per one-standard deviation increment of total anger expression was 1.77 (95% confidence interval 1.29-2.43) and 1.03 (95% confidence interval 0.64-1.66; P for interaction = 0.036) among retired and employed workers, respectively. CONCLUSIONS: A positive association between anger expression and the risk of cardiovascular disease was confined to retired workers, suggesting that continuing work after retirement age could reduce anger expression-related cardiovascular disease risk. Geriatr Gerontol Int 2024; 24: 385-389.

Association between smoking and height loss in Japanese workers: A retrospective study.

Height loss is reported to be an independent risk factor for all-cause and cardiovascular mortality. Smoking, which is responsible for a considerable proportion of deaths due to any cause, is also associated with lumbar disc degeneration, a major risk factor for height loss. Therefore, smoking could be an independent risk factor for height loss. To clarify the association between smoking status and height loss, a retrospective study with 8,984 (5,518 men and 3,466 women) Japanese workers was conducted. The present study population comprised 9,681 workers aged 40-74 years who participated in annual medical examinations between 2011 and 2017 (baseline). Subjects without a height measurement during 2012-2018 (endpoint) were excluded from the analysis (n = 697). Height loss was defined as being in the highest quartile of annul height decrease (1.48 mm/year for men and 1.79 mm/year for women). Independent of known cardiovascular risk factors, smoking was positively associated with height loss among men but not among women. With never smokers as the referent group, the adjusted odds ratio (95% confidence interval) was 1.15 (0.98, 1.35) for former smokers and 1.24 (1.05, 1.46) for current smokers among men, respectively. Among women, the corresponding values were 0.98 (0.79, 1.21) and 0.90 (0.71, 1.16), respectively. Since height loss and smoking are independent risk factors for all-cause and cardiovascular mortality, these results help clarify the mechanisms underlying the association between height loss and mortality risk.

Mushroom intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study (CIRCS).

It is uncertain whether dietary intake of mushrooms rich in dietary fibre and several antioxidants is associated with a lower risk of dementia. We sought to examine prospectively the association between mushroom intake and the risk of disabling dementia. We performed a prospective study involving 3750 people aged 40 to 64 years residing in three communities who participated in an annual cardiovascular risk survey from 1985 to 1999. Cases of incident disabling dementia were surveyed from 1999 to 2020. We calculated the hazard ratios (HR) and 95 % CI for incident total dementia according to mushroom intake among participants with or without a history of stroke. During a mean 16·0 years' follow-up in 3739 eligible participants, 670 people developed disabling dementia. For women, mushroom intake was inversely associated with the risk of total dementia and the association was confined to dementia without a history of stroke. The multivariable HR (95 % CI) for total dementia in women were 0·81 (0·62, 1·06) for mushroom intake of 0·1-14·9 g/d and 0·56 (0·42, 0·75) for mushroom intake above 15·0 g/d (Pfor trend = 0·003) compared with no intake. The corresponding HR (95 % CI) for dementia without a history of stroke were 0·66 (0·47, 0·93) and 0·55 (0·38, 0·79) (Pfor trend = 0·01). In men, no associations were observed between mushroom intake and the risk of disabling dementia. Among Japanese women, dietary mushroom intake was associated with a lower risk of disabling dementia.

Serum folate and risk of disabling dementia: a community-based nested case-control study.

PURPOSE: The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia). METHODS: We performed a nested case-control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. RESULTS: After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51-0.99), 0.76 (0.54-1.06), 0.70 (0.49-1.00), and 0.62 (0.43-0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke. CONCLUSION: In this nested case-control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals.

FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons.

MicroRNAs (miRNAs) modulate mRNA expression, and their deregulation contributes to various diseases including amyotrophic lateral sclerosis (ALS). As fused in sarcoma (FUS) is a causal gene for ALS and regulates biogenesis of miRNAs, we systematically analyzed the miRNA repertoires in spinal cords and hippocampi from ALS-FUS mice to understand how FUS-dependent miRNA deregulation contributes to ALS. miRNA profiling identified differentially expressed miRNAs between different central nervous system (CNS) regions as well as disease states. Among the up-regulated miRNAs, miR-1197 targets the pro-survival pseudokinase Trib2. A reduced TRIB2 expression was observed in iPSC-derived motor neurons from ALS patients. Pharmacological stabilization of TRIB2 protein with a clinically approved cancer drug rescues the survival of iPSC-derived human motor neurons, including those from a sporadic ALS patient. Collectively, our data indicate that miRNA profiling can be used to probe the molecular mechanisms underlying selective vulnerability, and TRIB2 is a potential therapeutic target for ALS.

HbA1c and height loss among Japanese workers: A retrospective study.

Evaluating the risk of height loss could be an efficient way to evaluate endothelial health, which might be associated with all-cause and cardiovascular mortality. Diabetes is an established risk factor both for intervertebral disk degeneration and osteoporosis-related fractures, which are major risk factors for height loss among adults. Therefore, hemoglobin A1c (HbA1c), as an indicator of the presence of diabetes, could be positively associated with height loss. A retrospective study of 10,333 workers aged 40 to 74 years was conducted. Height loss was defined as being in the highest quintile of height decrease per year. HbA1c in the normal range was positively associated with height loss. The known cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) for height loss with a 1-standard deviation (SD) increase in HbA1c (0.38% for both men and women) was 1.06 (1.02, 1.10) for men and 1.15 (1.07, 1.23) for women, respectively. When limit those analysis among those without diabetes, the magnitude was slightly higher; the fully adjusted OR and 95% CI for height loss with a 1-SD increase in HbA1c was 1.19 (1.11, 1.28) for men and 1.32 (1.20, 1.44) for women, respectively. Even when HbA1c is within the normal range, higher HbA1c is a significant risk factor for height loss among workers.

Association between anti-thyroid peroxidase antibody and thyroid stimulating hormone: a cross-sectional study.

To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH.

Association between serum albumin levels and height loss in Japanese workers: a retrospective study.

BACKGROUND: Height loss starting in middle age was previously shown to be associated with high cardiovascular mortality in later life. However, the factors associated with height loss remain unknown. Since low serum albumin levels are reported to be associated with high mortality caused by cardiovascular disease, they may also contribute to height loss. METHODS: To clarify the association between serum albumin and height loss, we conducted a retrospective study of 7637 Japanese workers who participated in general health check-ups from 2008 to 2019. Height loss was defined as the highest quartile of height loss per year. RESULTS: Individual with high serum concentration of albumin possess beneficial influence on preventing incidence of height loss. In both men and women, serum albumin level was significantly inversely associated with height loss. After adjustment for known cardiovascular risk factors, the adjusted odd ratio (OR) and 95% confidence interval (CI) for height loss per 1 standard deviation of albumin (0.2 g/dL for both men and women) were 0.92 (0.86, 0.98) in men and 0.86 (0.79, 0.95) in women. Even when the analysis was limited to participants without hypoalbuminemia, essentially same association was observed, with fully adjusted corresponding ORs (95%CI) of 0.92 (0.86, 0.98) in men and 0.86 (0.78, 0.94) in women. CONCLUSION: Independent of known cardiovascular risk factors, higher serum albumin levels may prevent height loss among Japanese workers. While several different diseases cause hypoalbuminemia, they may not be the main reasons for the association between serum albumin and height loss. Though further research is necessary, this finding may help clarify the mechanisms underlying the association between height loss and higher mortality in later life.

Progression of Carotid Intima-Media Thickness Partly Indicates the Prevention of Hypertension among Older Individuals in the General Population.

Structural atherosclerosis, as evaluated by carotid intima-media thickness (CIMT), is reported to be positively associated with hypertension. However, angiogenesis, which plays an important role in the progression of structural atherosclerosis, prevents hypertension by reducing peripheral vascular resistance. These associations evoke a contradiction: characteristics associated with the progression of structural atherosclerosis, which is related to hypertension, might prevent hypertension. To clarify novel mechanisms underlying the association between structural atherosclerosis and hypertension, multifaceted analyses are necessary. We performed several epidemiological studies based on this concept. This study summarizes those epidemiological studies and adds some discussion. Studies focusing on circulating CD34-positive cells, single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF), SNPs in BRACA1-associated protein (BRAP), platelets, human T-cell leukemia virus type 1 (HTLV-1), and SNPs in aldehyde dehydrogenase 2 (ALDH2) have shown that active endothelial repair, which leads to the progression of structural atherosclerosis, helps prevent hypertension. These associations indicate that the progression of structural atherosclerosis could act as a marker of angiogenesis, which reduces peripheral vascular resistance. In general, a positive association between structural atherosclerosis and hypertension has been reported. However, the progression of structural atherosclerosis could act as a marker of activity that prevents hypertension via reductions in peripheral vascular resistance.

Profile of Nagasaki Islands Study (NaIS): A Population-Based Prospective Cohort Study on Multi-disease.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow-up with them for vital status (death), migration, and occurrence of diseases such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1) -associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014-2016, secondary surveys during 2017-2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed-up; and 3,594 and 3,364 residents (aged 27-96 and 28-98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Serum Concentration of Growth Differentiation Factor 15 and Atherosclerosis among General Older Japanese Individuals with Normal Weight.

Growth differentiation factor 15 (GDF-15), which modulates cellular energy balance, is reported to be positively associated with cardiovascular disease. However, there have been no reports about the association between serum GDF-15 concentration and atherosclerosis as evaluated by carotid intima-media thickness (CIMT) among the general population. A cross-sectional study of 536 Japanese individuals aged 60 to 69 years was conducted. To avoid the influence of abnormal cellular energy balance, this study only included participants who had a normal body mass index (BMI) and normal thyroid hormone (free thyroxine and free triiodothyronine) levels. A significant positive association between serum GDF-15 concentration and atherosclerosis was observed. In the sex- and age-adjusted model (Model 1), the odds ratio (OR) (95% confidence interval (CI)) for the logarithmic value of GDF-15 and atherosclerosis was 2.62 (1.67, 5.87). This association remained after adjusting for thyroid function and renal function (Model 2) and further adjusting for known cardiovascular risk factors (Model 3). The corresponding values were 2.61 (1.15, 5.93) for Model 2 and 2.49 (1.08, 5.71) for Model 3, respectively. Serum GDF-15 concentrations could help us to estimate the risk of atherosclerosis by indicating the status of cellular energy balance, which is related to mitochondrial activity among comparative healthy older individuals.

ASO Author Reflections: Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Values in Patients with Pancreatic Cancer: Focusing on the Usefulness in Patients with Normal CA19-9.

Pancreatic cancer (PC) is one of the most aggressive cancer types, and carbohydrate antigen (CA) 19-9 has been the most useful biomarker for its surveillance and prognosis prediction. However, CA19-9 may not be sufficiently prognostic in some patients, such as Lewis antigen-negative phenotype (Le[a-b-]) patients who secrete little or no CA19-9. Duke pancreatic monoclonal antigen type 2 (DUPAN-2) has been proposed as a complementary marker to CA19-9 in PC patients, but its utility in Le(a-b-) patients has only been reported in a limited number of cases. In a retrospective analysis of 224 PC patients who underwent surgery, the present study investigated the utility of DUPAN-2 in combination with CA19-9. The study subjects were divided into three groups based on their CA19-9 and DUPAN-2 levels. The normal CA19-9/high DUPAN-2 group had significantly larger tumors and a higher frequency of microscopic vascular invasion, perineural invasion, and recurrence than the normal CA19-9/normal DUPAN-2 group. Both the disease-free survival and disease-specific survival (DSS) of patients in the normal CA19-9/high DUPAN-2 group were significantly shorter than those in the normal CA19-9/normal DUPAN-2 group, and comparable with those in the high CA19-9 group. The results suggest that DUPAN-2 may be useful as a complementary biomarker to CA19-9 in PC, especially in patients who have normal CA19-9 levels. However, since this was a single-center, retrospective study, multicenter studies are needed to confirm the findings and determine the optimal cut-off value for patients with normal CA19-9 levels.

Longitudinal trajectories of smoking status using 25 year annually-updated data and all-cause mortality followed over 30 years: A community-based prospective cohort study.

We aimed to evaluate the long-term risk of smoking for all-cause mortality according to smoking status trajectories using 25-year annually-repeated input, traced by group-based trajectory modeling with an extension to account for non-random participant attrition or truncation due to death. We examined 2682 men and 4317 women aged 40 to 59 years who participated in annual health checks for the community-based prospective cohort study, 1975-1984 enrollment in Japan. The main outcome measure was all-cause mortality (follow-up period: median 30.2 years in men and 32.2 years in women). We traced annual smoking trajectories, stratified by sex and smoking status at baseline. For smokers at baseline, we identified five trajectories in both sexes, with different patterns of smoking cessation (e.g., early quitters and lifelong smokers). We calculated HRs and 95% CI of all-cause mortality using Cox proportional hazards regression modeling adjusted for age, body mass index, alcohol intake, blood pressure category, dyslipidemia and glucose category. Compared with one-time-point-based smokers, trajectory-based lifelong smokers had an increased risk of all-cause mortality; HRs were 1.31 (95% CI, 1.18-1.46) in men and 1.26 (95% CI, 0.91-1.73) in women. Among community residents aged 40 to 59 years, 25-year-trajectory-based lifelong smokers had an approximately 30% increased risk for all-cause mortality compared to one-time-point-based smokers. Risk of all-cause mortality among smokers with earlier cessation varied materially. It is necessary to consider the trajectories of smoking status to clarify the long-term excess risk of smoking.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Levels in Patients with Pancreatic Cancer.

BACKGROUND: This study aimed to evaluate the clinical implication of Duke pancreatic monoclonal antigen type 2 (DUPAN-2) for patients with pancreatic cancer (PC), especially those with normal carbohydrate antigen (CA) 19-9 levels. METHODS: The study reviewed 224 patients who underwent surgery for PC from January 2003 through December 2019 at the Shizuoka Cancer Center. The patients were divided into three groups according to the following CA19-9 and DUPAN-2 levels: normal CA19-9/normal DUPAN-2, normal CA19-9/high DUPAN-2, and high CA19-9. The prognostic utility of the DUPAN-2 levels in the normal CA19-9 patients was investigated. RESULTS: Elevated serum levels of DUPAN-2 were observed in 29 (25.2%) of the normal CA19-9 patients. The cutoff value for serum DUPAN-2 level was set at 250 U/ml. Both disease-free survival and disease-specific survival (DSS) in the normal CA19-9/high DUPAN-2 group were significantly shorter than in the normal CA19-9/normal DUPAN-2 group and comparable with those in the high CA19-9 group. In the normal CA19-9 group, DUPAN-2 was identified as an independent prognostic factor for DSS. The patients with normal CA19-9/high DUPAN-2 had higher pathologic malignancy than the patients with normal CA19-9/normal DUPAN-2, which was comparable with that in the patients with high CA19-9. CONCLUSION: In PC, DUPAN-2 may be useful as a biomarker complementary with CA19-9. The combination of these two markers may aid in the preoperative prediction of prognosis for patients with PC.