Trends in the incidence of head and neck cancer: A nationwide population-based study.

OBJECTIVE: This study aimed to demonstrate the temporal trend in incidence of head and neck cancer (HNC) in Taiwan. MATERIALS AND METHODS: Patients with a HNC were retrieved from the Taiwan's Health Insurance Database. We identified 16,894 patients aged ≥20 years who had received a first-time diagnosis of cancer of the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, sinonasal, salivary gland or thyroid gland between 2010 and 2018. We calculated the annual incidence rate per 100,000 population, overall, and classified by gender and cancer type. We also used the annual percent change (APC) to characterize trends in head and neck cancer rates over time. RESULTS: The incidence rate showed a gradual decline during this period from 2010 to 2018 with an APC of -2.81% (p < 0.001). Within gender groups, the decline was not statistically significant among females (APC = -1.69, 95% CI = -3.58 âˆ¼ 0.23, p = 0.080). Within cancer types, strikingly high magnitude and statistically significant declines were observed in respect of cancer of the nasopharynx (APC = -7.89%, 95% CI = -9.43%∼-6.31%, p < 0.001), sinonasal cancer (APC = -10.08%, 95% CI = -16.66%∼-2.99%, p = 0.012) and oropharyneal cancer (APC = -9.47%, 95% CI = -15.15%∼-3.42%, p = 0.013) over the study period. In contrast, there was a statistically significant increase in incidence on thyroid cancer over the study period with an APC of 4.75% (95% CI = -2.81%∼6.75%, p < 0.001). CONCLUSIONS: HNCs in Taiwan are showing a decreasing trend, led by the upper respiratory and oropharyngeal cancers. However, there was a concurrent increasing trend of the incidence on thyroid cancer. These trends may be attributable to changing lifestyles and behavioral choices in Taiwan.

Prognostic Effect of Comorbid Disease and Immune Gene Expression on Mortality in Kidney Cancer-A Population Based Study.

The effect of comorbidities and the immune profiles of the kidney cancer microenvironment play a major role in patients' prognosis and survival. Using the National Health Insurance Research Database (Taiwan), we identified patients aged >20 years with a first diagnosis of kidney cancer between 2005 and 2014. Differences in demographic characteristics and comorbidities were examined using the Pearson chi-squared test or the t test. The Cox regression model was used to construct the nomogram. RNA-seq data were applied from The Cancer Genome Atlas database, and correlations between immune metagenes and clinical characteristics were determined using a linear regression model. In this nationwide cohort study, including 5090 patients with kidney cancer, predictors in our prediction models included age, sex, chronic kidney disease, dialysis requirements, renal stones, cerebrovascular disease, and metastasis tumor. In the tumor tissue profiles, significant positive correlations between immune metagenes and clinical stage or overall survival were observed among Natural Killer (NK) cells (CD56-), CD4+ T-helper 2 (Th2) cells, and activated Dendritic Cell (aDC). A negative correlation was observed between expression level of Dendritic Cell (DC) and overall survival. Patients with kidney cancer exhibit high prevalence of comorbid disease, especially in older patients. Comorbid disease types exert unique effects, and a particular comorbidity can affect cancer mortality. Moreover, the expression of immune metagenes can be utilized as potentialbiomarkers especially for further study of molecular mechanisms as well as microenvironments in kidney cancer.

Increased risk of cholesteatoma among patients with allergic rhinitis: A nationwide investigation.

OBJECTIVES: No large population-based studies have reported on the risk of cholesteatoma developing after allergic rhinitis (AR). This study used a nationwide population-based claims database to investigate the hypothesis that AR may increase the risk of cholesteatoma. STUDY DESIGN: Retrospective cohort study. METHODS: Data from Taiwan's Longitudinal Health Insurance Database were analyzed to compile the following: 1) 15,953 patients newly diagnosed with AR between 1997 and 2000, and 2) a comparison cohort of 63,812 matched non-AR enrollees (with a ratio of 1 to 4). Each patient was followed for 10 years to identify cases in which cholesteatoma subsequently developed. The Kaplan-Meier method was used to determine the cholesteatoma-free survival rate, and the log-rank test was used to compare survival curves. Cox proportional hazard regressions were performed to compute adjusted hazard ratios (HRs). RESULTS: Among the 79,765 patients enrolled in this study, 45 (159,364 person-years) from the AR cohort and 88 (638,130 person-years) from the comparison cohort were diagnosed with cholesteatoma during the follow-up period (incidence rates 0.28 and 0.14 of 1,000 person-years, respectively). Patients with AR were more likely to develop cholesteatoma compared to those without AR (adjusted HR 1.57, 95% confidence interval = 1.05-2.34, P < 0.05). Patients with AR presented a significantly lower 10-year cholesteatoma-free survival rate than did those in the comparison group (log-rank, P < 0.001). CONCLUSION: This is the first study to demonstrate a link between AR and the development of cholesteatoma. We suggest that clinicians keep this association in mind and carefully investigate the possibility of development of cholesteatoma among patients with AR. LEVEL OF EVIDENCE: 3b. Laryngoscope, 128:547-553, 2018.

Association Between Middle Ear Cholesteatoma and Chronic Rhinosinusitis.

Importance: Chronic rhinosinusitis (CRS) can cause an obstruction of the tubal orifice and thereby compromise ventilation of the middle ear. The resulting negative pressure in the middle ear may, in turn, lead to the formation of an eardrum retraction pocket and subsequent acquired cholesteatoma. This study hypothesizes that CRS may increase the risk of cholesteatoma. Objective: To evaluate the risk of cholesteatoma in patients with CRS. Design, Setting, and Participants: This study used a nationwide, population-based claims database to test the hypothesis that CRS may increase the risk of cholesteatoma. The Longitudinal Health Insurance Database of Taiwan was used to compile data from (1) 12 670 patients with newly diagnosed CRS between January 1, 1997, and December 31, 2002, and (2) a comparison cohort of 63 350 matched individuals without CRS, resulting in a CRS vs control ratio of 1:5. Data analysis was performed from June 1 to October 27, 2015. Each patient was followed up for 8 years to identify those in whom cholesteatoma subsequently developed. The Kaplan-Meier method was used to determine the cholesteatoma-free survival rate, and the log-rank test was used to compare survival curves. Cox proportional hazards regression models were used to compute the 8-year hazard ratios (HRs). Main Outcomes and Measures: Diagnosis of cholesteatoma. Results: Among the 76 020 patients enrolled in this study, 35 220 (46.3%) were female; mean (SD) age was 27.57 (22.03) years. A total of 209 patients developed cholesteatoma, 66 (101 084 person-years) individuals from the CRS cohort and 143 (506 540 person-years) from the comparison cohort were diagnosed with cholesteatoma during the 8-year follow-up period. The incidence of cholesteatoma per 1000 person-years was more than twice as high among patients with CRS (0.65; 95% CI, 0.50-0.81 person-years) than among those without CRS (0.28; 95% CI, 0.24-0.33). The absolute difference in the incidence density between CRS and non-CRS group was 0.37 (95% CI, 0.21-0.53) per 1000 patient-years. After adjusting for potential confounders, patients with CRS had a 69% increased risk of cholesteatoma within 8 years, compared with those without CRS (HR, 1.69; 95% CI, 1.23-2.32). Patients with CRS presented a significantly lower 8-year cholesteatoma-free survival rate than did those in the comparison group. The absolute difference in the 8-year cholesteatoma-free survival rate between the CRS and non-CRS groups was 0.0029 (95% CI, 0.0016-0.0043). Conclusions and Relevance: This is the first large-scale study, to date, to demonstrate a prospective link between CRS and the subsequent development of cholesteatoma within a follow-up period of 8 years. The purpose of the study was to draw attention to the possibility of development of cholesteatoma among patients with CRS. Because that possibility exists, clinicians should keep this association in mind as well as the importance of a thorough head and neck examination.

Does adding intraperitoneal paclitaxel to standard intraperitoneal regimen yield incremental survival? A propensity score-matched cohort study.

We recruited consecutive patients with stage III epithelial ovarian, tubal, and peritoneal cancers who had optimal residual tumor after primary cytoreductive surgery and who received intraperitoneal chemotherapy between 2002 and 2012. Two propensity score-matched sample cohorts were created. We found that the addition of paclitaxel as a second intraperitoneal agent on a 3-week dosing schedule did not yield significant incremental survival benefits over the intraperitoneal delivery of a single cisplatin-based regimen. If our findings could be confirmed by a prospective randomized study, then it would be interesting to explore the efficacy of shifting back to a dose-dense intraperitoneal delivery of paclitaxel or a dose-dense delivery of a new formulation of paclitaxel for the patients with stage III epithelial ovarian, tubal, and peritoneal cancers.

Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis.

BACKGROUND: In the analysis of survival data for cancer patients, the problem of competing risks is often ignored. Competing risks have been recognized as a special case of time-to-event analysis. The conventional techniques for time-to-event analysis applied in the presence of competing risks often give biased or uninterpretable results. METHODS: Using a prospectively collected administrative health care database in a single institution, we identified patients diagnosed with stage III or IV primary epithelial ovarian, tubal, and peritoneal cancers with minimal residual disease after primary cytoreductive surgery between 1995 and 2012. Here, we sought to evaluate whether intraperitoneal chemotherapy outperforms intravenous chemotherapy in the presence of competing risks. Unadjusted and multivariable subdistribution hazards models were applied to this database with two types of competing risks (cancer-specific mortality and other-cause mortality) coded to measure the relative effects of intraperitoneal chemotherapy. RESULTS: A total of 1263 patients were recruited as the initial cohort. After propensity score matching, 381 patients in each arm entered into final competing risk analysis. Cumulative incidence estimates for cancer-specific mortality were statistically significantly lower (p = 0.017, Gray test) in patients receiving intraperitoneal chemotherapy (5-year estimates, 34.5%; 95% confidence interval [CI], 29.5-39.6%, and 10-year estimates, 60.7%; 95% CI, 52.2-68.0%) versus intravenous chemotherapy (5-year estimates, 41.3%; 95% CI, 36.2-46.3%, and 10-year estimates, 67.5%, 95% CI, 61.6-72.7%). In subdistribution hazards analysis, for cancer-specific mortality, intraperitoneal chemotherapy outperforms intravenous chemotherapy (Subdistribution hazard ratio, 0.82; 95% CI, 0.70-0.96) after correcting other covariates. CONCLUSIONS: In conclusion, results from this comparative effectiveness study provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy even eliminating the confounding of competing risks. We suggest that implementation of competing risk analysis should be highly considered for the investigation of cancer patients who have medium to long-term follow-up period.

Depression and cholesteatoma: Preliminary findings from a nationwide population-based retrospective cohort study.

OBJECTIVE: To estimate the risk of developing depressive disorder (DD) following diagnosis with cholesteatoma. METHODS: In the study, we analyzed data from the Longitudinal Health Insurance Database of Taiwan. A total of 599 patients newly diagnosed with cholesteatoma between 1997 and 2007 were included with a comparison cohort of 2995 matched non-cholesteatoma enrollees. Each patient was followed for 3 years to identify the subsequent development of DD. Cox proportional hazard regression analysis was performed to compute adjusted 3-year hazard ratios. RESULTS: The incidence of DD per thousand person-years was approximately twice as high among patients with cholesteatoma (11.32) as among those without cholesteatoma (5.85). After adjusting for potential confounders, patients with cholesteatoma were 1.99 times (95% CI=1.18-3.34, P=0.010) more likely to suffer from DD within 3 years compared to those without cholesteatoma. CONCLUSIONS: This is the first study to demonstrate a link between cholesteatoma and subsequent DD within a three-year followup. We suggest that clinicians keep this critical but neglected issue in mind and carefully investigate the possibility of subsequent psychological problems among cholesteatoma patients.

The association between urbanization and rheumatoid arthritis in Taiwan.

OBJECTIVES: To investigate the association between rheumatoid arthritis (RA) and urbanization and compare the medication selection for RA patients in urban vs. rural areas. METHODS: RA patients were identified among 1,000,000 random individuals from a 23-million-person nationwide health insurance database, and controls were matched at a 1 : 10 ratio. Taiwan's 359 townships were grouped into 7 urbanization levels. Geographic region and monthly income were also analyzed. Medication use in the most urbanized and less-urbanized areas were also compared. RESULTS: Rural dwellers had lower odds of having an RA diagnosis. The odds ratio (OR) for level 5 area residents of having an RA diagnosis was 0.62 (95% confidence interval (CI) 0.46 - 0.85; p = 0.002), and they were both 0.76 for level 6 - 7 area residents (95% CI, 0.61 - 0.95 for level 6; p = 0.017 and 0.60 - 0.96 for level 7; p = 0.021) compared to level 1 (the most urban dwellers). The ORs of having a new RA diagnosis were 0.57 (95% CI 0.41 - 0.79, p = 0.001) in eastern Taiwan and 0.33 (95% CI 0.15 - 0.69, p = 0.004) on offshore islands compared to northern Taiwan. No association was found between monthly income and RA. Urban-dwelling RA patients used more tumor necrosis factor-α antagonists (level 1 urbanization; n = 24; 2.3%) than RA patients in less-urbanized areas (level 2 - 7 urbanization n = 30; 1.3%; p = 0.038). CONCLUSION: Results of this study suggested that an RA diagnosis and treatment are associated with urbanization.

Increased association between endometriosis and endometrial cancer: a nationwide population-based retrospective cohort study.

OBJECTIVE: Association between endometriosis and ovarian cancer has been well established. Nonetheless, endometriosis may also be associated with endometrial cancer because of shared etiological mechanisms of both estrogen stimulation and chronic inflammation; however, the association between these 2 disorders has rarely been investigated. METHODS: The National Health Insurance Research Databases in Taiwan were retrieved and analyzed. The case cohort consisted of patients with a diagnosis of endometriosis between January 1997 and December 2000 (N = 15,488). For the construction of control cohort, 8 age- and sex-matched control patients for every patient in the case cohort were selected using a random sampling method (n = 123,904). All subjects were tracked for 10 years from the date of entry to identify whether they had developed endometrial cancer. The Cox proportional hazards regression model was used to evaluate 10-year event occurrence of endometrial cancer. RESULTS: During the 10-year follow-up period, 392 participants developed endometrial cancer, with 104 (0.7%) distributed in the case cohort and 288 (0.2%) in the control cohort. Multivariable Cox regression modeling demonstrates a higher risk for developing endometrial cancer in the case cohort than in the control cohort (adjusted hazard ratio [aHR], 2.83; 95% confidence interval [CI], 1.495.35; P < 0.01). Age at diagnosis of endometriosis shows a moderator effect: when 40 years or younger, the risk for developing endometrial cancer was comparable between the case cohort and the control cohort (aHR, 1.42; 95% CI, 0.55-3.70; P = 0.226), whereas when older than 40 years, the risk for developing endometrial cancer was higher in the former group than in the latter group (aHR, 7.08; 95% CI, 2.33-21.55; P = 0.007). CONCLUSIONS: Patients diagnosed with endometriosis may harbor an increased risk for developing endometrial cancer in their later life. Closer monitoring is advised for this patient population.

Applying data mining for the analysis of breast cancer data.

Data mining, also known as Knowledge-Discovery in Databases (KDD), is the process of automatically searching large volumes of data for patterns. For instance, a clinical pattern might indicate a female who have diabetes or hypertension are easier suffered from stroke for 5 years in a future. Then, a physician can learn valuable knowledge from the data mining processes. Here, we present a study focused on the investigation of the application of artificial intelligence and data mining techniques to the prediction models of breast cancer. The artificial neural network, decision tree, logistic regression, and genetic algorithm were used for the comparative studies and the accuracy and positive predictive value of each algorithm were used as the evaluation indicators. 699 records acquired from the breast cancer patients at the University of Wisconsin, nine predictor variables, and one outcome variable were incorporated for the data analysis followed by the tenfold cross-validation. The results revealed that the accuracies of logistic regression model were 0.9434 (sensitivity 0.9716 and specificity 0.9482), the decision tree model 0.9434 (sensitivity 0.9615, specificity 0.9105), the neural network model 0.9502 (sensitivity 0.9628, specificity 0.9273), and the genetic algorithm model 0.9878 (sensitivity 1, specificity 0.9802). The accuracy of the genetic algorithm was significantly higher than the average predicted accuracy of 0.9612. The predicted outcome of the logistic regression model was higher than that of the neural network model but no significant difference was observed. The average predicted accuracy of the decision tree model was 0.9435 which was the lowest of all four predictive models. The standard deviation of the tenfold cross-validation was rather unreliable. This study indicated that the genetic algorithm model yielded better results than other data mining models for the analysis of the data of breast cancer patients in terms of the overall accuracy of the patient classification, the expression and complexity of the classification rule. The results showed that the genetic algorithm described in the present study was able to produce accurate results in the classification of breast cancer data and the classification rule identified was more acceptable and comprehensible.

Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study.

BACKGROUND: Hypoxia plays an important role in the development of solid tumors. Intermittent hypoxia is the hallmark of sleep apnea (SA). We tested the hypothesis that SA may increase the risk of breast cancer in Taiwan by using a population-based data set. METHODS: Our study cohort consisted of women diagnosed with SA between January 2003 and December 2005 (n = 846). For each SA patient, five age-matched control women were randomly selected as the comparison cohort (n = 4230). All participant cases were followed for 5 years from the index date to identify the development of breast cancer. Cox proportional-hazards regression was performed to evaluate the 5-year breast-cancer-free survival rates. RESULTS: Forty-four women developed breast cancer during the 5-year follow-up period, among whom 12 were SA patients and 32 were in the comparison cohort. The adjusted hazard ratio (HR) of breast cancer in patients with SA was higher [HR, 2.09; 95% confidence interval (CI), 1.06-4.12; P < 0.05] than that of the controls during the 5-year follow-up. Despite not meeting statistical significance, we found increases in the risk of breast cancer in women aged 30-59 years (HR, 2.06; 95% CI, 0.90-4.70) and ≥60 years (HR, 3.05; 95% CI, 0.90-10.32) compared with those aged 0-29 years. CONCLUSION: The findings of our population-based study suggest an association between SA and an increased risk of breast cancer in women.

Increased risk of benign prostate hyperplasia in sleep apnea patients: a nationwide population-based study.

BACKGROUND: Sleep apnea (SA) is a common sleep disorder characterized by chronic intermittent hypoxia (IH). Chronic IH induces systemic inflammatory processes, which can cause tissue damage and contribute to prostatic enlargement. The purpose of this study was to evaluate the association between benign prostate hyperplasia (BPH) and SA in a Taiwanese population. METHODS: The study population was identified from Taiwan's National Health Insurance Research Database (NHIRD) and contained 202 SA patients and 1010 control patients. The study cohort consisted of men aged ≥ 30 years who were newly diagnosed with SA between January 1997 and December 2005. Each patient was monitored for 5 years from the index date for the development of BPH. A Cox regression analysis was used to calculate the hazard ratios (HRs) for BPH in the SA and control patients. RESULTS: During the 5-year follow-up, 18 SA patients (8.9%) and 32 non-SA control patients (3.2%) developed BPH. The adjusted HR for BPH was 2.35-fold higher in the patients with SA than in the control patients (95% confidence interval (CI) 1.28-4.29, P<.01). We further divided the SA patients into 4 age groups. After adjusting for potential confounding factors, the highest adjusted HR for BPH in the SA patients compared with the control patients was 5.59 (95% CI = 2.19-14.31, P<.001) in the patients aged between 51 and 65 years. CONCLUSION: Our study results indicate that patients with SA are associated with increased longitudinal risk of BPH development, and that the effects of SA on BPH development are age-dependent.

A longitudinal cohort study of incidence rates of inguinal hernia repair in 0- to 6-year-old children.

BACKGROUND/PURPOSE: This study provides epidemiologic data on the incidence of inguinal hernia repair in preschool children using the Taiwan National Health Insurance Research Database. We believe that the data on hernia repair in said database provide a close approximation of the true incidence of inguinal hernia in young children. METHOD: A cohort of 1,073,891 deidentified individuals was randomly selected from an insured population of 23 million. Subjects born during the period 1997-2004 were followed from birth to 6 years. The chi-square test and logistic regression modeling were used for statistical analyses. RESULT: A total of 92,308 individuals were born during the study period. Of these individuals, 3881 underwent hernia repairs. The cumulative incidence of hernia repair in children aged 0 to 6 years was 4.20%/7 years. The boy/girl ratio was 4.27:1 and the unilateral/bilateral ratio was 3.77:1. The incidence of hernia repair among boys was highest during the first year of life, but then decreased with age. In contrast, the incidence among girls remained stable during the first 6 years of life. Boys younger than 1 year had more bilateral repairs than boys in other age groups (p<0.0001) and girls had significantly more bilateral repairs than boys (p<0.0001). Subjects with a history of preterm birth also had a higher incidence of hernia repair than subjects who were born at full term (odds ratio=2.34, p<0.0001). CONCLUSION: Yearly incidence of hernia repair was obtained from a nationwide database. Some of the observations have not been reported elsewhere.

The association between gender and outcome of patients with upper tract urothelial cancer.

The incidence of upper tract urothelial cancer (UTUC) has gradually increased over the past 30 years. Although most reports have shown that UTUC occurs more frequently in men than in women, women have been found to have a worse prognosis than men. In Taiwan, a high incidence of UTUC has been reported, with an unusual minor predominance of female cases. The purpose of this study was to determine the influence of gender on the outcome of patients with UTUC after nephroureterectomy and bladder cuff excision. From January 1990 to December 2007, 301 patients diagnosed with UTUC were admitted at our institution. A retrospective analysis of the effect of gender on the clinical outcome was performed. We compared the 5-year bladder recurrence-free, progression-free, and disease-specific survival rates. While we did not observe any differences between men and women in bladder recurrence-free, progression-free, or disease-specific survival rates, we found that female patients had a significantly higher percentage of contralateral recurrence than the males (5.9% vs. 0.8%, p = 0.019).

Cox-2 gene overexpression in ureteral stump urothelial carcinoma following nephrectomy for renal cell carcinoma: a case report.

INTRODUCTION: A primary ureteral stump tumor after a nephrectomy is rare; urothelial carcinoma of the ureteral stump after a nephrectomy for renal cell carcinoma is even rarer. A thorough review of the literature indicated that only seven cases have previously been reported. In this study, we report the first Taiwanese case of urothelial carcinoma of the ureteral stump after a nephrectomy. It is also the first female case in the literature. The relationship between inflammatory genes, medication history and ureteral stump carcinoma after a nephrectomy for renal cell carcinoma has not been reported. CASE PRESENTATION: A 72-year-old Asian Taiwanese women with chronic hepatitis C, liver cirrhosis and chronic kidney disease underwent a hand-assisted laparoscopic radical nephrectomy in 2001 due to renal cell carcinoma. Nine years later, she was diagnosed with ureteral stump urothelial carcinoma. Genetic and medication surveys were performed. Importantly, our patient had taken Chinese herbal drugs for more than 10 years and the inflammatory gene, Cox-2, was highly expressed in this patient. This is the first report to study the relationship between the Cox-2 gene and ureteral stump carcinoma after a nephrectomy for renal cell carcinoma. CONCLUSION: Long-term multiple use of Chinese herbal drugs could be one of the important risk factors for developing urothelial cancer. Close functional coupling between Chinese herbal drugs, Cox-2 gene activation and urothelial cancer should be further investigated.