The Utility of a "Second-Look" Debridement Following Endonasal Skull Base Surgery in the Pediatric Population.

Background Sinonasal debridement is typically performed in the weeks following endonasal skull base surgery (ESBS). In the pediatric population, this second-look procedure may require general anesthesia; however, there is currently little evidence assessing the benefit of this practice. Methods This was a multicenter retrospective study of pediatric patients (age <18 years) undergoing a planned second-look debridement under general anesthesia following ESBS. Intraoperative findings, interventions performed, and perioperative complications were reviewed. Multivariate regression analysis was performed to identify associations between intraoperative findings and clinical factors. Results We reviewed 69 cases of second-look debridements (age mean 8.6 ± 4.2 years, range: 2-18 years), occurring a mean of 18.3 ± 10.3 days following ESBS. All abnormal findings were noted in patients age ≤12 years. Synechiae were noted in 8.7% of cases, bacterial rhinosinusitis in 2.9%, and failed reconstruction with cerebrospinal fluid leak in 4.5% (two cases of flap malposition and one case of flap necrosis). All failed reconstructions were noted following expanded endonasal cases for craniopharyngioma, and in each case, a revision reconstruction was performed during the second-look surgery. Synechiae were not significantly associated with younger age, revision cases, or cases with reconstructive flaps. There were no perioperative complications. Conclusion Second-look debridement under general anesthesia may be useful in the identification and intervention of sinonasal pathology following endoscopic skull base surgery, particularly in children ≤12 years old or those with pedicled flap reconstructions. Larger controlled studies are warranted to validate this practice and refine indications and timing of this second procedure.

Uncovering a dose-response relationship between positive fecal immunochemical test (FIT) and all-cause, cardiovascular and cancer-related mortality.

BACKGROUND: Fecal immunochemical test (FIT) is for colorectal cancer (CRC) screening. Its association with non-CRC mortality has been overlooked. Given the quantitative FIT values, its dose-response relationships with different causes of deaths and years of life shortened were assessed. METHODS: This retrospective study included 546,214 adults aged ≥ 20 who attended a health surveillance program from 1994 to 2017 and were followed up until the end of 2020. FIT ≥ 20 µg Hb/g was defined as positive. The Cox model was used to assess adjusted hazard ratios (aHR). RESULTS: Positive FIT was associated with increased all-cause mortality (aHR: 1.34, 95 % CI: 1.25-1.44) and all-cancer mortality (aHR: 1.71, 95 % CI: 1.55-1.89), with a reduction of life expectancy by 4 years. The association remained even with CRC excluded. With each 10 µg Hb/g increase in FIT above 20 µg Hb/g, life expectancy was reduced by one year, and mortality increased by 4 %. About 18.6 % of deaths with positive FIT were attributed to cardiovascular disease (CVD), followed by CRC (13.5 %) and upper gastrointestinal (GI) cancers (4.5 %). The all-cause mortality rate after excluding CRC for positive FIT was 3.56/1,000 person-year, comparable to the all-cause mortality rate of 3.69/1,000 person-year for hypertension. CONCLUSION: Positive FIT was associated with increased mortality in a dose-response manner and shortened life expectancy by 4 years, an overlooked risk comparable to hypertension, even with CRC excluded. After a negative colonoscopy, subjects with positive FIT should undergo a workup on CVD risk factors and look for other upper GI cancers.

Introducing Surgical Equity into Contemporary Medical Education: Results From Operation Equity, a Pilot Curriculum.

OBJECTIVE: To date, education about health equity for early-stage healthcare trainees is largely situated outside of surgical disciplines. This study aims to evaluate the effectiveness of a surgical equity curriculum offered to a voluntary group of medical and graduate students. DESIGN: Mixed-methods cohort study from January to June 2021. Pre- and post-course surveys measured domains of attitudes, self-reported confidence, and knowledge via 5-point Likert scale and multiple-choice questions. Paired t tests were used to analyze quantitative responses. Qualitative responses were studied via iterative thematic analysis. SETTING: At the University of Pennsylvania in Philadelphia, PA which provides tertiary level, institutional care, 10, interdisciplinary 1.5-hour sessions were held over 1 semester, teaching surgical equity topics that spanned the peri-operative continuum. PARTICIPANTS: Twenty-four medical and graduate students from across the University of Pennsylvania enrolled. Twenty completed both surveys. RESULTS: From pre- to post-course, students improved across all domains. Students improved in their self-rated ability to identify strategies to talk about sensitive health topics with patients (pre: 20%, post: 90%) and identify strategies to address healthcare disparities in surgery (pre: 10%, post: 90%). Qualitatively, from pre- to post-course, more students could articulate the role of bias and identify opportunities for surgeons to engage in surgical equity. The course strengthened any pre-existing interest in surgical equity, and for 1 student, created interest in a surgical career where it had not previously existed. Many also expressed greater resolve to provide patient-centric care. CONCLUSIONS: Formal curricula can improve students' ability to advocate for surgical equity. A similar framework may fill a need for medical students interested in health equity and surgical careers at other institutions.

Management of Chronic Sialadenitis due to Sjogren's Syndrome and Radioactive Iodine Therapy Using Sialendoscopy.

INTRODUCTION: Sialendoscopy is a minimally invasive technique for the management of salivary gland disease. This work characterizes its utility for treating chronic sialadenitis due to Sjogren's syndrome and radioactive iodine (RAI) therapy. METHODS: A single-center, retrospective review of patients undergoing sialendoscopy between March 2013 and May 2019 for the treatment of chronic sialadenitis due to Sjogren's or prior RAI therapy was performed. RESULTS: Thirty-four patients with Sjogren's and 25 patients who received RAI were identified, undergoing a total of 86 procedures. Median age at presentation was 53 years with mean follow-up time of 14.3 months. Seventy-two procedures were performed on the parotid gland, four on the submandibular gland, and ten on both glands. Corticosteroid injection and duct dilation were performed most commonly. Sixteen patients required repeat procedure. All patients were symptomatically improved at follow-up visit. DISCUSSION/CONCLUSION: These results support the idea that sialendoscopy offers symptomatic benefit for patients with chronic sialadenitis due to Sjogren's or RAI.

Association of Sugar-Sweetened Beverages and Cardiovascular Diseases Mortality in a Large Young Cohort of Nearly 300,000 Adults (Age 20-39).

(1) Background: The association of sugar-sweetened beverages (SSBs) with cardiovascular disease (CVD) mortality in younger adults (age 20−39) is rarely mentioned in the literature. Younger adults are less vulnerable to CVDs, but they tend to consume more SSBs. This prospective study aimed to assess the association between CVD mortality and SSBs in younger adults between 1994 and 2017. (2) Methods: The cohort enrolled 288,747 participants consisting of 139,413 men and 148,355 women, with a mean age 30.6 ± 4.8 years, from a health surveillance program. SSBs referred to any drink with real sugar added, such as fructose corn syrup or sucrose. One serving of SSB contains about 150 Kcal of sugar in 12 oz of drink. Cox models were used to estimate the mortality risk. (3) Results: There were 391 deaths from CVDs in the younger adults, and the positive association with CVD mortality started when SSB intake was ≥2 servings/day (HR: 1.59, 95% CI: 1.16−2.17). With mortalities from diabetes and kidney disease added to CVDs, the so-called expanded CVD mortality risk was 1.49 (95% CI: 1.11−2.01). By excluding CVD risk factors (hypertension, diabetes, and smoking), the CVD mortality risk increased to 2.48 (95% CI: 1.33−4.62). The dose−response relationship persisted (p < 0.05 for trend) in every model above. (4) Conclusions: Higher intake of SSBs (≥2 servings/day) was associated with increased CVD mortality in younger adults. The younger adults (age 20−39) with SSB intake ≥2 servings/day had a 50% increase in CVD mortality in our study, and the mortality risk increased up to 2.5 times for those without CVD risk factors. The dose−response relationship between the quantity of SSB intake and the mortality risk of CVD in younger adults discourages SSB intake for the prevention of CVD mortality.

"Sugar-Sweetened Beverages" Is an Independent Risk From Pancreatic Cancer: Based on Half a Million Asian Cohort Followed for 25 Years.

Although the link between sugar-sweetened beverages (SSB) and pancreatic cancer has been suggested for its insulin-stimulating connection, most epidemiological studies showed inconclusive relationship. Whether the result was limited by sample size is explored. This prospective study followed 491,929 adults, consisting of 235,427 men and 256,502 women (mean age: 39.9, standard deviation: 13.2), from a health surveillance program and there were 523 pancreatic cancer deaths between 1994 and 2017. The individual identification numbers of the cohort were matched with the National Death file for mortality, and Cox models were used to assess the risk. The amount of SSB intake was recorded based on the average consumption in the month before interview by a structured questionnaire. We classified the amount of SSB intake into 4 categories: 0-<0.5 serving/day, ≥0.5-<1 serving per day, ≥1-<2 servings per day, and ≥2 servings per day. One serving was defined as equivalent to 12 oz and contained 35 g added sugar. We used the age and the variables at cohort enrolment as the reported risks of pancreatic cancers. The cohort was divided into 3 age groups, 20-39, 40-59, and ≥60. We found young people (age <40) had higher prevalence and frequency of sugar-sweetened beverages than the elderly. Those consuming 2 servings/day had a 50% increase in pancreatic cancer mortality (HR = 1.55, 95% CI: 1.08-2.24) for the total cohort, but a 3-fold increase (HR: 3.09, 95% CI: 1.44-6.62) for the young. The risk started at 1 serving every other day, with a dose-response relationship. The association of SSB intake of ≥2 servings/day with pancreatic cancer mortality among the total cohort remained significant after excluding those who smoke or have diabetes (HR: 2.12, 97% CI: 1.26-3.57), are obese (HR: 1.57, 95% CI: 1.08-2.30), have hypertension (HR: 1.90, 95% CI: 1.20-3.00), or excluding who died within 3 years after enrollment (HR: 1.67, 95% CI: 1.15-2.45). Risks remained in the sensitivity analyses, implying its independent nature. We concluded that frequent drinking of SSB increased pancreatic cancer in adults, with highest risk among young people.

Sialendoscopy for sialodocholithiasis following submandibular gland excision: six variations on a theme.

Sialendoscopy is a minimally invasive technique that facilitates the diagnosis and treatment of sialolithiasis. This case series presents the novel use of sialendoscopy to treat sialodocholithiasis in six patients with a non-functional or surgically absent submandibular gland by a single surgeon at the University of Pennsylvania Health System between March 2013 and December 2019. The four female and two male patients had a median age of 56 years and mean follow-up of 16.2 months (range 1-44.5). All stones were successfully removed using sialendoscopy, and in 5 patients a combined approach was utilized. All patients remain asymptomatic at last clinical follow-up. We conclude that sialendoscopy is a viable, minimally invasive method for managing sialodocholithiasis in patients with prior submandibular gland excision or atretic gland. It is also useful as an assistive tool when approaching complex transcervical or transoral procedures in previously instrumented patients.

Converting health risks into loss of life years - a paradigm shift in clinical risk communication.

For facilitating risk communication in clinical management, such a ratio-based measure becomes easier to understand if expressed as a loss of life expectancy. The cohort, consisting of 543,410 adults in Taiwan, was recruited between 1994 and 2008. Health risks included lifestyle, biomarkers, and chronic diseases. A total of 18,747 deaths were identified. The Chiang's life table method was used to estimate a loss of life expectancy. We used Cox regression to calculate hazard ratios (HRs) for health risks. The increased mortality from cardio-metabolic risks such as high cholesterol (HR=1.10), hypertension (HR=1.48) or diabetes (HR=2.02) can be converted into a loss of 1.0, 4.4, and 8.9 years in life expectancy, respectively. The top 20 of the 30 risks were associated with a loss of 4 to 10 years of life expectancy, with 70% of the cohort having at least two such risk factors. Smoking, drinking, and physical inactivity each had 5-7 years loss. Individuals with diabetes or an elevated white count had a loss of 7-10 years, while prolonged sitting, the most prevalent risk factor, had a loss of 2-4 years. Those with diabetes (8.9 years) and proteinuria (9.1 years) present at the same time showed a loss of 16.2 years, a number close to the sum of each risk. Health risks, expressed as life expectancy loss, could facilitate risk communication. The paradigm shift in expressing risk intensity can help set public health priorities scientifically to promote a focus on the most important ones in primary care.

Assessment of music experience after cochlear implantation: A review of current tools and their utilization.

OBJECTIVE: To provide an overview of the current available music assessment tools after cochlear implantation (CI); to report on the utilization of music assessments in the literature; to propose potential future directions in music assessment after CI. METHODS: A thorough search was performed in PubMed, Embase, and The Cochrane Library through October 31, 2020. MeSH search terms, keywords, and phrases included "cochlear implant," "cochlear prosthesis," "auditory prosthesis," "music," "music assessment," "music questionnaire," "music perception," "music enjoyment, and "music experience." Potentially relevant studies were reviewed for inclusion, with particular focus on assessments developed specifically for the cochlear implant population and intended for widespread use. RESULTS/CONCLUSIONS: Six hundred and forty-three studies were screened for relevance to assessment of music experience among cochlear implantees. Eighty-one studies ultimately met criteria for inclusion. There are multiple validated tools for assessment of music experience after cochlear implantation, each of which provide slightly differing insights into the patients' subjective and/or objective post-activation experience. However, no single assessment tool has been adopted into widespread use and thus, much of the literature pertaining to this topic evaluates outcomes non-uniformly, including single-use assessments designed specifically for the study at hand. The lack of a widely accepted universal tool for assessment of music limits our collective understanding the contributory and mitigating factors applicable to current music experience of cochlear implantees, and limits our ability to uniformly evaluate the success of new implant technologies or music training paradigms.

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men.

BACKGROUND: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. METHODS: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. RESULTS: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). CONCLUSIONS: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Nuances and Management of Hilar Submandibular Sialoliths With Combined Transoral Robotic Surgery-Assisted Sialolithotomy and Sialendoscopy.

OBJECTIVE: To describe the management, technical nuances, and success rates of transoral robotic surgery (TORS)-assisted sialolithotomy. STUDY DESIGN: Retrospective database review. SETTING: Quaternary academic medical center. METHODS: Between the months of January 2015 and May 2019, patients with hilar submandibular gland stones underwent 2 main variations of TORS-assisted sialolithotomy and sialendoscopy: (1) TORS followed by sialendoscopy for patients with palpable predominantly single stones and (2) either sialendoscopy followed by TORS and sialendoscopy or sialendoscopy followed by TORS only for patients with nonpalpable or multiple stones. Clinical charts were reviewed to collect data, including stone size (imaging review, intraoperative measurement), palpability, duration of operation, TORS variation, operative challenges, symptom improvement, gland preservation rate, and complications. RESULTS: Thirty-seven patients were identified. Patients were 26 to 80 years old (mean, 57.2 years), and 40.5% were female. Twenty-four patients (64.9%) underwent TORS followed by sialendoscopy; 10 (27.0%), sialendoscopy followed by TORS and sialendoscopy; and 3 (8.1%), sialendoscopy followed by TORS only. The mean stone size was 12.4 mm (range, 4-28 mm). Eleven patients had multiple stones with a mean 4 stones per patient (range, 2-9). Procedural success was 91.9% (34/37) at a mean follow-up of 34.2 weeks (range, 1.4-262.1), and the gland preservation rate was 97.3% (36/37). No patients reported symptoms of lingual nerve injury at 3-month follow-up. CONCLUSION: TORS combined with sialendoscopy for hilar submandibular gland sialolithiasis allows for improved visualization of critical anatomy, tissue manipulation, and operative flexibility. In our experience, the operative success rate is high, and duration of surgery compares favorably with conventional combined hilar approaches.

Robotic Management of Salivary Glands.

There are numerous salivary gland pathologies for which robotic surgery can provide benefit. This article reviews the primary indications for use of transoral robotic surgery for salivary gland neoplasms. It also discusses transoral and retroauricular robotic approaches for pathology of the submandibular gland and prestyloid parapharyngeal space. These approaches have the advantage of avoiding a visible scar and are additionally minimally invasive in other ways as well. Robotic surgery offers advantages in several different modules of salivary gland surgery, similar to those it offers for oropharyngeal cancer, including improved optics, manual dexterity, and teamwork.

Single-port transoral robotic combined approach with sialendoscopy for sialolithiasis: Case report and review of the literature.

BACKGROUND: The da Vinci single-port (SP) is utilized in transoral robotic surgery (TORS) procedures for malignant oropharyngeal tumors. We report a case utilizing the da Vinci SP in TORS for sialolith removal. METHODS AND RESULTS: A 75-year-old male with chronic right submandibular gland (SMG) sialadenitis underwent combined da Vinci SP TORS approach with sialendoscopy for multiple SMG sialoliths. We were unable to find a previous report of using the da Vinci SP in TORS for SMG sialolith removal. CONCLUSION: The da Vinci SP has been utilized in a combined TORS approach with sialendoscopy for SMG sialolith removal. The da Vinci SP's additional arm provides improved retraction, enabling optimal visualization, dissection, and preservation of important structures such as the lingual nerve.

Loss of Life Expectancy by 10 Years or More From Elevated Aspartate Aminotransferase: Finding Aspartate Aminotransferase a Better Mortality Predictor for All-Cause and Liver-Related than Alanine Aminotransferase.

OBJECTIVES: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2 commonly ordered liver function tests, and ALT has long been considered more liver-specific than AST. Between the 2, the one which is better in predicting liver or non-liver-related mortality remains unsettled. METHODS: The cohort, 416,122 adults, came from a self-paying comprehensive health surveillance program during 1994-2008 and was followed up till 2008. Mortality came from National Death Index, with 10,412 deaths identified. Hazard ratios (HRs), computed by Cox model, and life expectancy, by life table method, were presented for 5 levels of AST and ALT with elevated AST or ALT defined as ≥40 IU/L. Liver disease included liver cancer and other liver conditions. RESULTS: There were 3 times more elevated ALT (15.4%) than AST (5.7%). However, those with elevated AST had higher mortality for all-cause (HR = 2.44), for liver disease (HR = 27.2), and for liver cancer (HR = 47.6) than its ALT counterparts (HR = 1.69, 10.8, and 20.2, respectively). Elevated AST also lost more years of life expectancy (10.2) than those lost by ALT (5.2) and larger than most common risks. Elevated AST had increased mortality from all cancers (HR = 3.57), stroke (HR = 1.36), respiratory diseases (HR = 1.34), and injuries (HR = 1.82), other than just liver disease. All-cause mortality remained significantly increased, when high risk groups were excluded, such as frequent drinkers, hepatitis carriers, those died from nonmedical conditions, those died in the first 3 years, or advanced fibrosis index based on 4 factors or aspartate transaminase-to-platelet ratio index. Results were consistent between those returned for second visits and those analyzed in initial visits. DISCUSSION: Those with elevated AST (≥40 IU/L) had life expectancy cut short by 10.2 years, doubled the number of years lost with elevated ALT. For all-cause and for liver-related mortality, AST was an important predictor, better than ALT.

Cancer risk associated with chronic diseases and disease markers: prospective cohort study.

OBJECTIVES: To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. DESIGN: Prospective cohort study. SETTING: Standard medical screening program in Taiwan. PARTICIPANTS: 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. MAIN OUTCOME MEASURES: Cancer incidence and cancer mortality. RESULTS: A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk associated with chronic diseases and markers was attenuated by 48% for cancer incidence and 27% for cancer mortality. CONCLUSIONS: Chronic disease is an overlooked risk factor for cancer, as important as five major lifestyle factors combined. In this study, chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death. Physical activity is associated with a nearly 40% reduction in the cancer risk associated with chronic diseases.

Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan.

The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840-0.862), with never smokers 0.806 (95% CI = 0.790-0.819), light smokers 0.847 (95% CI = 0.824-0.871), and heavy smokers 0.732 (95% CI = 0.708-0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF25-75%), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives.

The Role of Physical Activity in Harm Reduction among Betel Quid Chewers from a Prospective Cohort of 419,378 Individuals.

OBJECTIVE: To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing. METHODS: The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day. Physical activity of each individual, based on "MET-hour/week", was classified as "inactive" or "active", where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated. RESULTS: Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing. CONCLUSIONS: Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.

ABO blood types and cancer risk--a cohort study of 339,432 subjects in Taiwan.

BACKGROUND: The associations of laboratory-based ABO phenotypes with cancer risks and mortality have not been systematically determined. METHODS: The study subjects were 339,432 healthy individuals with laboratory-based blood types from a Taiwan cohort. RESULTS: Compared to blood type O, blood type A was significantly associated with an elevated risk of stomach cancer incidence (Hazard Ratio [HR], 1.38 [95% CI, 1.11-1.72]) and mortality (HR, 1.38 [95% CI, 1.02-1.86]) compared with blood type O, after adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and body mass index. Non-O blood types were associated with an elevated risk of pancreatic cancer, with blood type B reaching statistical significance for incidence (HR, 1.59 [95% CI, 1.02-2.48]) and mortality (HR, 1.63 [95% CI, 1.02-2.60]). In contrast, kidney cancer risk was inversely associated with blood type AB (HR, 0.41 [95% CI, 0.18-0.93]) compared to type O. CONCLUSION: Cancer risks vary in people with different ABO blood types, with elevated risks of stomach cancer associated with blood type A and pancreatic cancer associated with non-O blood types (A, B, and AB).

The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling.

PURPOSE: We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers. EXPERIMENTAL DESIGN: We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case-control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort composed of 425,660 participants. RESULTS: Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (<0.75 mg/dL) had 55% and 66% increase in risks of lung cancer incidence and mortality, respectively. For every 0.1 mg/dL decrease of bilirubin, the risks for lung cancer incidence and mortality increased by 5% and 6% in male smokers, respectively (both P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (Pinteraction = 0.001). CONCLUSION: Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer.

High serum iron is associated with increased cancer risk.

Epidemiologic studies linking high serum iron with cancer risks are limited and inconclusive, despite evidence implicating body iron in human carcinogenesis. A cohort of 309,443 adults in Taiwan who had no history of cancer had serum iron levels tested at the time of recruitment (1997-2008). Initially measured iron levels were associated with subsequent cancer risk by linking individuals with the National Cancer Registry and National Death File. HRs were calculated by the Cox model. One third of males (35%) and one fifth of females (18%) had high serum iron (≥120 µg/dL), which was associated with a 25% increase in risk for incidence of all cancers [HR, 1.25; 95% confidence interval (CI), 1.16-1.35] and with a 39% increase in risk for mortality from all cancers (HR, 1.39; 95% CI, 1.23-1.57). The relationship between serum iron and cancer risk was a J-shaped one, with higher cancer risk at both ends, either at lower than 60 µg/dL or higher than 120 µg/dL. At the higher end, cancer risk increased by 4% for every 10 µg/dL increment above 80 µg/dL, showing a dose-response relationship, with 60 to 79 µg/dL as a reference level. In a sensitivity analysis, the increases in risk were still observed after the first 5 years of cancer cases were excluded. Liver cancer risk was increased in HBV (-) non-hepatitis B carrier (3-fold) and HBV (+) hepatitis B carrier (24-fold). Lifestyle risks such as smoking, drinking, or inactivity interacted synergistically with high serum iron and significantly increased the cancer risks. The liver (HR, 2.49; 95% CI, 1.97-3.16) and the breast (HR, 1.31; 95% CI, 1.01-1.70) were the two major cancer sites where significant cancer risks were observed for serum iron either ≥120 µg/dL or ≥140 µg/dL, respectively. This study reveals that high serum iron is both a common disorder and a marker of increased risk for several cancers.