Ching-Chih Lee

Chronic Kidney Disease Itself Is a Causal Risk Factor for Stroke beyond Traditional Cardiovascular Risk Factors: A Nationwide Cohort Study in Taiwan

Background Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association. Methods We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (nu200a=u200a1393) and an age-matched control cohort of patients hospitalized for appendectomies (nu200a=u200a1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors. Results There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45–2.60; p<0.001) based on Cox regression and a 1.68-fold greater risk for stroke (95% CI, 1.25–2.25; pu200a=u200a0.001) based on propensity score. This was still the case for two cohorts younger than 75 years old and without traditional cardiovascular risk factors. Conclusions This study of Taiwanese patients indicates that CKD itself is a causal risk factor for stroke beyond the traditional cardiovascular risk factors. Primary CKD patients have higher risk for stroke than the general population and all CKD patients, irrespective of the presence or severity of traditional cardiovascular risk factors, should be made aware of the stroke risk and monitored for stroke prevention.

Multivariate analyses to assess the effects of surgeon and hospital volume on cancer survival rates: a nationwide population-based study in Taiwan.

Background Positive results between caseloads and outcomes have been validated in several procedures and cancer treatments. However, there is limited information available on the combined effects of surgeon and hospital caseloads. We used nationwide population-based data to explore the association between surgeon and hospital caseloads and survival rates for major cancers. Methodology A total of 11677 patients with incident cancer diagnosed in 2002 were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity scores were used to assess the relationship between 5-year survival rates and different caseload combinations. Results Based on the Cox proportional hazard model, cancer patients treated by low-volume surgeons in low-volume hospitals had poorer survival rates, and hazard ratios ranged from 1.3 in head and neck cancer to 1.8 in lung cancer after adjusting for patients’ demographic variables, co-morbidities, and treatment modality. When analyzed using the propensity scores, the adjusted 5-year survival rates were poorer for patients treated by low-volume surgeons in low-volume hospitals, compared to those treated by high-volume surgeons in high-volume hospitals (P<0.005). Conclusions After adjusting for differences in the case mix, cancer patients treated by low-volume surgeons in low-volume hospitals had poorer 5-year survival rates. Payers may implement quality care improvement in low-volume surgeons.

Age-Adjusted Charlson Comorbidity Index Scores as Predictor of Survival in Colorectal Cancer Patients Who Underwent Surgical Resection and Chemoradiation

Abstract We studied the effect of Age-Adjusted Comorbidity Index Score in colorectal cancer patients who underwent similarly aggressive treatment. Using the National Health Insurance Research Database of Taiwan, we identified 5643 patients with colorectal cancer who underwent surgical resection and chemoradiation from 2007 through 2011. We estimated survival according to Age-Adjusted Comorbidity Index Scores and 5-year survival using Cox proportional hazard regression analysis, adjusting for sex, oxaliplatin-based chemotherapy, socioeconomic status, geographic region, and hospital characteristics. In the cohort were 3230 patients with colonic cancer and 2413 patients with rectal cancer, who had undergone combined surgical resection and either neoadjuvant or adjuvant chemoradiation. After adjusting for patient characteristics (sex, oxaliplatin-based chemotherapy, socioeconomic status, geographic region, and hospital-characteristics), colonic cancer patients with age-adjusted Charlson (AAC) ≥6 had a 106% greater risk of death within 5 years (adjusted HRu200a=u200a2.06; 95% CI, 1.66–2.56). In rectal cancer patients, patients with an AAC score of 4–5 had a 28% greater risk of death within 5 years (adjusted HRu200a=u200a1.28; 95% CI, 1.02–1.61), and those with AAC ≥6 had a 47% greater risk (adjusted HRu200a=u200a1.47; 95% CI, 1.15–1.90). Age and burden of comorbidities influence survival of patients with colonic or rectal cancer. Age-Adjusted Comorbidity Score remains an independent prognostic factor even after adjusting for the aggressiveness of treatment.

Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study.

BackgroundIncreased risk of ischemic stroke has been validated for several cancers, but limited study evaluated this risk in cervical cancer patients. Our study aimed to evaluate the risk of ischemic stroke in cervical cancer patients.MethodsThe study analyzed data from the 2003 to 2008 National Health Insurance Research Database (NHIRD) provided by the National Health Research Institutes in Taiwan. Totally, 893 cervical cancer patients after radiotherapy and 1786 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of ischemic stroke.ResultsThe 5-year cumulative risk of ischemic stroke was significantly higher for the cervical cancer group than for the control group (7.8% vs 5.1%; p <0.005). The risk of stroke was higher in younger (age <51xa0years) than in older (age ≥51 years) cervical cancer patients (HRu2009=u20092.73, pu2009=u20090.04; HRu2009=u20091.37, pu2009=u20090.07) and in patients with more than two comorbid risk factors (5xa0years cumulative stroke rate of two comorbidities: 15% compared to no comorbidities: 4%).ConclusionsThese study demonstrated cervical cancer patients had a higher risk of ischemic stroke than the general population, especially in younger patients. Strategies to reduce this risk should be assessed.

Monocyte Chemotactic Protein 1 (MCP-1) Modulates Pro-Survival Signaling to Promote Progression of Head and Neck Squamous Cell Carcinoma

Background Monocyte chemotactic protein-1 (MCP-1) recruits monocytes and macrophages to inflammation sites, and inflammatory infiltration correlates with the progression of head and neck squamous cell carcinoma (HNSCC). This study aims to determine whether MCP-1 expression is related to HNSCC malignancy and patient survival. We also investigated the relationship between MCP-1 expression and the phosphorylation state of the pro-survival pathway factors Akt, ERK, and STAT3. Methods Expression of MCP-1 and related proteins in HNSCC cell lines was investigated using western blotting. HNSCC patients (34) without distant metastasis at diagnosis were recruited for tissue specimen evaluation of MCP-1 expression and clinical outcomes. The relationship between MCP-1 expression and survival was evaluated using the Cox proportional hazard model with stepwise selection. Results High-grade HNSCC cell lines were found to have higher levels of active Akt, ERK, and/or STAT3 than did lower grade cell lines under serum-free condition. OCSL, the most malignant cell line, had the highest level of endogenous MCP-1. Administration of exogenous recombinant MCP-1 increased phosphorylation of Akt, ERK, and STAT3 in a dose- and time-dependent manner and increased cellular resistance to serum starvation. Inhibition of Akt, ERK, or STAT3 reduced cell growth and caused cell death. Long-term survival of HNSCC patients was negatively associated with the histological intensity of MCP-1, implicating MCP-1 as a potential prognostic marker for HNSCC. Conclusions These results suggest that overexpressed MCP-1 in cancer cells may promote HNSCC progression through upregulating pro-survival signaling pathways. High cellular MCP-1 expression is related to poor overall survival rate in HNSCC patients.

The combined effects of hospital and surgeon volume on short-term survival after hepatic resection in a population-based study.

Background The influence of different hospital and surgeon volumes on short-term survival after hepatic resection is not clearly clarified. By taking the known prognostic factors into account, the purpose of this study is to assess the combined effects of hospital and surgeon volume on short-term survival after hepatic resection. Methods 13,159 patients who underwent hepatic resection between 2002 and 2006 were identified in the Taiwan National Health Insurance Research Database. Data were extracted from it and short-term survivals were confirmed through 2006. The Cox proportional hazards model was used to assess the relationship between survival and different hospital, surgeon volume and caseload combinations. Results High-volume surgeons in high-volume hospitals had the highest short-term survivals, following by high-volume surgeons in low-volume hospitals, low-volume surgeons in high-volume hospitals and low-volume surgeons in low-volume hospitals. Based on Cox proportional hazard models, although high-volume hospitals and surgeons both showed significant lower risks of short-term mortality at hospital and surgeon level analysis, after combining hospital and surgeon volume into account, high-volume surgeons in high-volume hospitals had significantly better outcomes; the hazard ratio of other three caseload combinations ranging from 1.66 to 2.08 (p<0.001) in 3-month mortality, and 1.28 to 1.58 (p<0.01) in 1-year mortality. Conclusions The combined effects of hospital and surgeon volume influenced the short-term survival after hepatic resection largely. After adjusting for the prognostic factors in the case mix, high-volume surgeons in high-volume hospitals had better short-term survivals. Centralization of hepatic resection to few surgeons and hospitals might improve patients’ prognosis.

Haptoglobin Polymorphism as a Risk Factor for Chronic Kidney Disease: A Case-Control Study

Aims: Taiwan has the highest incidence and prevalence of end-stage renal disease worldwide. Haptoglobin (Hp) has a role in renal protection, and there are known differences in the function of different Hp alleles. We aim to study the association between Hp genotype and chronic kidney disease (CKD) in Taiwan. Methods: We performed one hospital-based, age-matched case-control study of 213 patients with CKD and 213 controls to evaluate the association between Hp polymorphism and CKD. Three major Hp genotypes were determined using polymerase chain reaction and electrophoresis. An unconditional logistic regression model was used to identify the associated risk factors for the development of CKD. Results: The frequency of Hp2-2 genotype and Hp2 allele was significantly higher in the CKD group than in controls (p = 0.032 and 0.024, respectively). After adjustment for covariates, the Hp2-2 genotype (vs. Hp1-1; OR 3.841) remained significantly associated with the development of CKD, together with diabetes (OR 3.131), hypertension (OR 1.748) and dyslipidemia (OR 1.646). Conclusion: This present study shows that Hp2-2 genotype is an independent risk factor for CKD. Determination of the Hp genotype may be of potential value to the prediction of genetic risk for CKD.

Higher caseload improves cervical cancer survival in patients treated with brachytherapy

ObjectivesIncreased caseload has been associated with better patient outcomes in many areas of health care, including high-risk surgery and cancer treatment. However, such a positive volume vs. outcome relationship has not yet been validated for cervical cancer brachytherapy. The purpose of this study was to examine the relationship between physician caseload and survival rates in cervical cancer treated with brachytherapy using population-based data.MethodsBetween 2005 and 2010, a total of 818 patients were identified using the Taiwan National Health Insurance Research Database. Multivariate analysis using a Cox proportional hazards model and propensity scores was used to assess the relationship between 5-year survival rates and physician caseloads.ResultsAs the caseload of individual physicians increased, unadjusted 5-year survival rates increased (P = 0.005). Using a Cox proportional hazard model, patients treated by high-volume physicians had better survival rates (P = 0.03), after adjusting for comorbidities, hospital type, and treatment modality. When analyzed by propensity score, the adjusted 5-year survival rate differed significantly between patients treated by high/medium-volume physicians vs. patients treated by low/medium-volume physicians (60% vs. 54%, respectively; P = 0.04).ConclusionsProvider caseload affected survival rates in cervical cancer patients treated with brachytherapy. Both Cox proportional hazard model analysis and propensity scores showed association between high/medium volume physicians and improved survival.

High Incidence of Ischemic Stroke Occurrence in Irradiated Lung Cancer Patients: A Population-Based Surgical Cohort Study

Background and Purpose A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients. Methods A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (nu200a=u200a112) and surgery-alone (nu200a=u200a448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint. Results Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, Pu200a=u200a0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44–12.22; Pu200a=u200a0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001). Conclusions A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged.

The association of socioeconomic status and access to low-volume service providers in breast cancer.

Background No large-scale study has explored the combined effect of patients’ individual and neighborhood socioeconomic status (SES) on their access to a low-volume provider for breast cancer surgery. The purpose of this study was to explore under a nationwide universal health insurance system whether breast cancer patients from a lower individual and neighborhood SES are disproportionately receiving breast cancer surgery from low-volume providers. Methods 5,750 patients who underwent breast cancer surgery in 2006 were identified from the Taiwan National Health Insurance Research Database. The Cox proportional hazards model was used to compare the access to a low-volume provider between the different individual and neighborhood SES groups after adjusting for possible confounding and risk factors. Hosmer-Lemeshow goodness-of-fit statistic was used to determine how well the model fit the data. Results Univariate analysis data shows that patients in disadvantaged neighborhood were more likely to receive breast cancer surgery at low-volume hospitals; and lower-SES patients were more likely to receive surgery from low-volume surgeons. In multivariate analysis, after adjusting for patient characteristics, the odds ratios of moderate- and low-SES patients in disadvantaged neighborhood receiving surgery at low-volume hospitals was 1.47 (95% confidence interval=1.19-1.81) and 1.31 (95% confidence interval=1.05-1.64) respectively compared with high-SES patients in advantaged neighborhood. Moderate- and low-SES patients from either advantaged or disadvantaged neighborhood had an odds ratios ranging from 1.51 to 1.80 (p<0.001) to receiving surgery from low-volume surgeons. In Hosmer-Lemeshow goodness-of-fit test, p>0.05 that shows the model has a good fit. Conclusions In this population-based cross-sectional study, even under a nationwide universal health insurance system, disparities in access to healthcare existed. Breast cancer patients from a lower individual and neighborhood SES are more likely to receive breast cancer surgery from low-volume providers. The authorities and public health policies should keep focusing on these vulnerable groups.