Effectiveness of 23-valent pneumococcal polysaccharide vaccine on elderly patients with colorectal cancer: A population-based propensity score-matched cohort study.

The commonly used vaccine for adults with a high risk of pneumonia is 23-valent pneumococcal polysaccharide vaccine (PPSV23). However, its effectiveness in patients with colorectal cancer has not been investigated. This study aimed to investigate the effectiveness of PPSV23 in reducing the risk of pneumonia among elderly patients with colorectal cancer.A total of 120,605 newly diagnosed patients with colorectal cancer were identified from the Taiwan National Health Insurance Research Database between 1996 and 2010. Of these patients, 18,468 were 75 years or older in 2007 to 2010, and 3515 received PPSV23. People aged 75 years or older have been considered eligible for receiving PPSV23 vaccination in Taiwan since 2007. The specific "vaccination period" of October 2008 to December 2008 was used to minimize the potential immortal time bias. Therefore, 893 patients who received PPSV23 outside this vaccination period or died before 2009 and 2960 unvaccinated patients who died before 2009 were excluded. After the propensity score was matched with a 1:3 ratio, 2622 vaccinated patients and 7866 unvaccinated patients were recruited. A multivariate log-linear Poisson regression model was performed and adjusted for potential confounders, including influenza vaccination, vaccination period, cancer treatment modalities, comorbidities, and sociodemographic variables.After 2 years of follow-up, the incidence rate of the pneumonia hospitalization of the vaccinated patients was significantly lower than that of the unvaccinated patients at 85.53 per 1000 person-years (PYs) of the former and 92.38 per 1000 PYs of the latter. The proportions of patients who had 2, 3, and >3 pneumonia hospitalizations per year were consistently lower in the vaccinated group than in the unvaccinated group (1.9% vs 2.0%, 0.5% vs 0.9%, and 0.7% vs 1.1%, respectively). After adjustment for covariates was made, PPSV23 vaccine was significantly associated with a reduced risk of pneumonia hospitalization, with an adjusted incidence rate ratio of 0.88 (P = .040). The overall pneumonia-free survival rate was also significantly higher in the vaccinated patients than in the unvaccinated patients (P = .001).PPSV23 vaccination was associated with a significantly reduced rate of pneumonia hospitalization in elderly patients with colorectal cancer.

Risks of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache.

Tinnitus and hearing impairment are prevalent among headache patients. This study aims to investigate the risk of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache. Participants included 43 294 patients with non-migraine headache (non-migraine headache cohort) and 173 176 patients with no headache of any type (control cohort) frequency-matched with respect to 10-year age interval and sex from the Longitudinal Health Insurance Database 2005 of the Taiwan National Health Insurance Research Database. The mean age of the non-migraine headache cohort was 28.4 ± 14.9 years, and 58.5% of this cohort was male. The incidence rates of tinnitus, sensorineural hearing impairment, and sudden deafness were compared between cohorts using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used to examine the association of tinnitus, sensorineural hearing impairment, and sudden deafness with non-migraine headache, with adjustment for all covariates. The combined risk of either tinnitus, sensorineural hearing impairment, or sudden deafness was higher in the non-migraine headache cohort than in the control cohort (adjusted odds ratio [aHR], 2.73; 95% confidence interval [95% CI], 2.62-2.84; p < 0.0001). Subgroup analysis showed that patients in the non-migraine headache cohort were at significantly higher risk of developing tinnitus (aHR, 3.05; 95% CI, 2.91-3.19; p < 0.0001), sensorineural hearing impairment (aHR, 1.89; 95% CI, 1.74-2.05; p < 0.0001), and sudden deafness (aHR, 2.14; 95% CI, 1.77-2.59; p < 0.0001) than were controls. In this population-based study, the risks of tinnitus, sensorineural hearing impairment, and sudden deafness were found to be significantly higher in patients with non-migraine headache than in those without headache.

Anti-hepatitis C virus therapy in chronic kidney disease patients improves long-term renal and patient survivals.

BACKGROUND: Hepatitis C virus (HCV) infection is a documented risk factor for chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). However, to date there are no reports on the long-term hard endpoints (ESRD and death) of anti-HCV therapy [interferon-based therapy (IBT) or new direct-acting antivirals] in CKD patients. Direct-acting antivirals are not available in Taiwan's single-payer national health insurance database currently released for research. Therefore, we hypothesized that a retrospective analysis of the long-term outcomes of IBT in CKD patients will serve as a proxy for direct-acting antivirals to increase our understanding of progression to ESRD following HCV infection. AIM: To evaluate the long-term outcomes (ESRD and death) of anti-HCV therapy, especially IBT, in HCV-infected patients with stage 1-5 CKD. METHODS: We analyzed 93894 Taiwanese adults diagnosed with CKD and without HBV infection. Of these, 4.9% were infected with HCV. Of the 4582 HCV-infected CKD patients, 482 (10.5%) received IBT (treated cohort). They were matched 1:4 with 1928 untreated HCV-infected CKD patients (untreated cohort) by propensity scores and year, which further matched 1:2 by propensity scores with 3856 CKD patients without HCV infection (uninfected cohort). All participants were followed until the occurrence of ESRD, death, or the end of 2012. The association between HCV infection, IBT use, and risks of ESRD and death was analyzed using competing risk analysis. RESULTS: Taking the uninfected cohort as a reference, the adjusted hazard ratios for ESRD, after adjusting for competing mortality, were 0.34 (0.14-0.84, P = 0.019) and 1.28 (1.03-1.60, P = 0.029) in the treated and untreated cohorts, respectively. The treated cohort had a 29% (0.54-0.92, P = 0.011) decrease in mortality compared to the untreated cohort, in which the mortality was 31% (1.18-1.45, P < 0.001) higher than in the uninfected cohort. The reduced risks of ESRD (0.14, 0.03-0.58, P = 0.007) and death (0.57, 0.41-0.79, P = 0.001) were greatest in HCV-infected CKD patients who received at least 4 mo of IBT, which accounted for 74% of the treated cohort. CONCLUSION: Adequate anti-HCV therapy in CKD patients improves long-term renal and patient survival.

Risk of rheumatoid arthritis in patients with hepatitis C virus infection receiving interferon-based therapy: a retrospective cohort study using the Taiwanese national claims database.

OBJECTIVES: To illuminate the association between interferon-based therapy (IBT) and the risk of rheumatoid arthritis (RA) in patients infected with hepatitis C virus (HCV). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This retrospective cohort study used Taiwan's Longitudinal Health Insurance Database 2005 that included 18 971 patients with HCV infection between 1 January 1997 and 31 December 2012. We identified 1966 patients with HCV infection who received IBT (treated cohort) and used 1:4 propensity score-matching to select 7864 counterpart controls who did not receive IBT (untreated cohort). OUTCOME MEASURES: All study participants were followed until the end of 2012 to calculate the incidence rate and risk of incident RA. RESULTS: During the study period, 305 RA events (3.1%) occurred. The incidence rate of RA was significantly lower in the treated cohort than the untreated cohort (4.0 compared with 5.5 per 1000 person-years, p<0.018), and the adjusted HR remained significant at 0.63 (95% CI 0.43 to 0.94, p=0.023) in a Cox proportional hazards regression model. Multivariate stratified analyses revealed that the attenuation in RA risk was greater in men (0.35; 0.15 to 0.81, p=0.014) and men<60 years (0.29; 0.09 to 0.93, p=0.036). CONCLUSIONS: This study demonstrates that IBT may reduce the risk of RA and contributes to growing evidence that HCV infection may lead to development of RA.

Association of Tinnitus and Other Cochlear Disorders With a History of Migraines.

Importance: A headache is a symptom of a migraine, but not all patients with migraine have headaches. It is still unclear whether a migraine might increase the risk of cochlear disorders, even though a migraine does not occur concurrently with cochlear disorders. Objective: To investigate the risk of cochlear disorders for patients with a history of migraines. Design, Setting, and Participants: This study used claims data from the Taiwan Longitudinal Health Insurance Database 2005 to identify 1056 patients with migraines diagnosed between January 1, 1996, and December 31, 2012. A total of 4224 controls were also identified from the same database based on propensity score matching. Statistical analysis was performed from January 23, 1996, to December 28, 2012. Main Outcomes and Measures: The incidence rate of cochlear disorders (tinnitus, sensorineural hearing impairment, and/or sudden deafness) was compared between the cohorts by use of the Kaplan-Meier method. The Cox proportional hazards regression model was also used to examine the association of cochlear disorders with migraines. Results: Of the 1056 patients with migraines, 672 were women and 384 were men, and the mean (SD) age was 36.7 (15.3) years. Compared with the nonmigraine cohort, the crude hazard ratio for cochlear disorders in the migraine cohort was 2.83 (95% CI, 2.01-3.99), and the adjusted hazard ratio was 2.71 (95% CI, 1.86-3.93). The incidence rates of cochlear disorders were 81.4 (95% CI, 81.1-81.8) per 1 million person-years for the migraine cohort and 29.4 (95% CI, 29.2-29.7) per 1 million person-years for the nonmigraine cohort. The cumulative incidence of cochlear disorders in the migraine cohort (12.2%) was significantly higher than that in the matched nonmigraine cohort (5.5%). Subgroup analysis showed that, compared with the nonmigraine cohort, the adjusted hazard ratios in the migraine cohort were 3.30 (95% CI, 2.17-5.00) for tinnitus, 1.03 (95% CI, 0.17-6.41) for sensorineural hearing impairment, and 1.22 (95% CI, 0.53-2.83) for sudden deafness. Conclusions and Relevance: In this population-based study, the risk of cochlear disorders, especially for tinnitus, was found to be significantly higher among patients with a history of migraines. This finding may support the presence and/or concept of "cochlear migraine."

Effectiveness of 23-valent pneumococcal polysaccharide vaccine on elderly long-term cancer survivors: a population-based propensity score matched cohort study.

OBJECTIVE: The Advisory Committee on Immunization Practices in 2012 recommended the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults with high risk of pneumonia. However, its effectiveness in cancer survivors has not been investigated. Our aim was to investigate the effectiveness of PPSV23 in these patients. DESIGN: Population-based matched cohort study. SETTING: Claim data were obtained from 1 million people registered with the National Health Insurance Research Database in 1996, and followed to 2010. People aged ≥75 years are eligible for receiving PPSV23 vaccination in Taiwan since 2007. PARTICIPANTS: Among the 30 249 patients with cancer, 6784 patients were 75 years or older eligible for PPSV23 vaccination. Among them, 1887 survived 5 or more years (ie, cancer survivors) after cancer diagnosis. We identified 377 cancer survivors who received PPSV23. A total of 754 propensity score matched unvaccinated patients were randomly selected. INTERVENTION: PPSV23 vaccination. PRIMARY OUTCOME MEASURES: The primary outcome was pneumonia hospitalisation. Potential confounders include influenza vaccination, vaccination period, cancer treatment modalities, comorbidities and sociodemographic variables. RESULTS: After 2 years of follow-up, vaccinated patients had a significantly lower incidence rate of pneumonia hospitalisation at 73.66 per 1000 person-years (PYs), compared with 117.82 per 1000 PYs for unvaccinated patients. Additionally, the prevalence for pneumonia hospitalisation frequency of >0-1,>1-2,>2-3 and >3 times per PY was all consistently lower in the vaccinated group (6.63% vs 9.28%, 1.86% vs 2.52%, 0.80% vs 1.59% and 0.27% vs 0.53%, respectively). After adjustment for covariates, PPSV23 vaccine was significantly associated with reduced pneumonia hospitalisation risk, with an adjusted incidence rate ratio of 0.695 (p=0.030). While the cumulative pneumonia incidence was also significantly lower in the vaccinated patients (p=0.027), the overall survival time was similar (p=0.136). CONCLUSIONS: PPSV23 vaccination was associated with a significantly reduced rate of pneumonia hospitalisation in long-term cancer survivors.

Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwanese chronic kidney disease patients acquiring hepatitis B virus infection.

AIM: To investigate the risk of end-stage renal disease (ESRD) in hepatitis B virus (HBV)-infected patients with chronic kidney disease (CKD) with and without nucleos(t)ide analogue (NA) therapy. METHODS: This nationwide cohort study included 103444 Taiwanese CKD adults without hepatitis C virus infection from the Taiwan Longitudinal Health Insurance Database 2005 between 1997 and 2012. We identified 2916 CKD patients who acquired HBV infection and did not receive NAs (untreated cohort), and they were propensity-matched 1:4 with 11664 uninfected counterparts. We also identified 442 CKD patients who acquired HBV infection and received NAs (treated cohort), and they were propensity-matched 1:3 with 1326 untreated counterparts. The association between HBV infection, NA use, and ESRD was analyzed using competing risk analysis. RESULTS: Multivariable Cox regression analysis showed a 1.67-fold higher risk (P < 0.0001) of ESRD in the untreated cohort (16-year cumulative incidence, 10.1%) than in the matched uninfected cohort (16-year cumulative incidence, 6.6%), which was independent of cirrhosis or diabetes. The treated cohort (16-year cumulative incidence, 2.2%) had an 87% lower ESRD risk (P < 0.0001) compared with the matched untreated cohort (16-year cumulative incidence, 11.9%). The number needed to treat for one fewer ESRD after NA use at 12 years was 12. Multivariable stratified analyses verified these associations in all subgroups. CONCLUSION: This study suggests that untreated HBV infection and NA therapy are associated with increased and decreased risk of ESRD, respectively, in CKD patients. Identification of HBV status and targeted monitoring for ESRD development are important in CKD patients living in HBV-endemic areas.

Irradiation enhanced risks of hospitalised pneumonopathy in lung cancer patients: a population-based surgical cohort study.

OBJECTIVE: Pulmonary radiotherapy has been reported to increase a risk of pneumonopathy, including pneumonitis and secondary pneumonia, however evidence from population-based studies is lacking. The present study intended to explore whether postoperative irradiation increases occurrence of severe pneumonopathy in lung cancer patients. DESIGN, SETTING AND PARTICIPANTS: The nationwide population-based study analysed the Taiwan National Health Insurance Research Database (covered >99% of Taiwanese) in a real-world setting. From 2000 to 2010, 4335 newly diagnosed lung cancer patients were allocated into two groups: surgery-RT (n=867) and surgery-alone (n=3468). With a ratio of 1:4, propensity score was used to match 11 baseline factors to balance groups. INTERVENTIONS/EXPOSURES: Irradiation was delivered to bronchial stump and mediastinum according to peer-audited guidelines. OUTCOMES/MEASURES: Hospitalised pneumonia/pneumonitis-free survival was the primary end point. Risk factors and hazard effects were secondary measures. RESULTS: Multivariable analysis identified five independent risk factors for hospitalised pneumonopathy: elderly (>65 years), male, irradiation, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Compared with surgery-alone, a higher risk of hospitalised pneumonopathy was found in surgery-RT patients (HR, 2.20; 95% CI, 1.93-2.51; 2-year hospitalised pneumonia/pneumonitis-free survival, 85.2% vs 69.0%; both p<0.0001), especially in elderly males with COPD and CKD (HR, 13.74; 95% CI, 6.61-28.53; p<0.0001). Unexpectedly, we observed a higher risk of hospitalised pneumonopathy in younger irradiated-CKD patients (HR, 13.07; 95% CI, 5.71-29.94; p<0.0001) than that of elderly irradiated-CKD patients (HR, 4.82; 95% CI, 2.88-8.08; p<0.0001). CONCLUSIONS: A high risk of hospitalised pneumonopathy is observed in irradiated patients, especially in elderly males with COPD and CKD. For these patients, close clinical surveillance and aggressive pneumonia/pneumonitis prevention should be considered. Further investigations are required to define underlying biological mechanisms, especially for younger CKD patients.

Enhancing clinical effectiveness of pre-radiotherapy workflow by using multidisciplinary-cooperating e-control and e-alerts: A SQUIRE-compliant quality-improving study.

Radiotherapy (RT) is useful in managing cancer diseases. In clinical practice, early initiation of RT is crucial for enhancing tumor control. But, delivering precise RT requires a series of pre-RT working processes in a tight staff-cooperation manner. In this regard, using information system to conduct e-control and e-alerts has been suggested to improve practice effectiveness; however, this effect is not well defined in a real-world RT setting.We designed an information system to perform e-control and e-alerts for the whole process of pre-RT workflow to shorten processing time, to improve overall staff satisfaction, and to enhance working confidence.A quality-improving study conducted in a large RT center.Externally validated data were retrospectively analyzed for comparison before (from Sep. 2012 to Dec. 2012, n = 223) and after (from Sep. 2013 to Dec. 2013, n = 240) implementation of pre-RT e-control and e-alerts.Applying the e-control with delay-working e-alerts in pre-RT workflow was the main intervention.Nine workstations were identified in pre-RT workflow. The primary outcome measure was the processing time in each pre-RT workstations before and after implementing the e-control and e-alerts. Secondary measures were staff-working confidence and near-missing cases during the process of pre-RT workflow.After implementing e-control, overall processing time of pre-RT workflow was shortened from 12.2 days to 8.9 days (P < .001). Follow-up data (till Jul. 2016) showed a durable effect of 9.2 days, being still below the predefined threshold of <10 days.Using a multidisciplinary-cooperating information system is useful to conduct e-control and e-alerts in the whole process of pre-RT workflow. Clinical effectiveness, staff satisfaction, and working confidence are able to be enhanced obviously.

Pelvic inflammatory disease increases the risk of a second primary malignancy in patients with cervical cancer treated by surgery alone.

As the number of long-term cervical cancer survivors continues to increase because of improvements in treatment, concerns about second primary malignancy have grown. The high-risk area of second primary cancers in cervical cancer survivors is the pelvis. Pelvic inflammatory disease (PID) could be a useful marker for gynecological cancers. Thus, we designed a large-scale, nationwide, controlled cohort study to investigate whether PID or other risk factors increased the risk of second primary cancers in patients with cervical cancer treated by surgery alone.Between 2000 and 2010, a total of 24,444 cervical cancer patients were identified using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan. Patients who received definite surgery were selected. To exclude the effect on second primary malignancy by treatment modalities, all cervical patients who ever having received adjuvant or definite radiotherapy or chemotherapy for primary cervical cancer were excluded. Finally, 3860 cervical cancer patients treated by surgery alone without adjuvant treatments were analyzed.Cox proportional hazards model was used for multivariate analysis and the Kaplan-Meier method was used to assess the cumulative risks. Regarding the incidence of second primary cancers, the standardized incidence ratio (SIR) was used.The median follow-up time was 56.6 months. The 6-year cumulative risk of second primary cancers is 0.16% and 0.12% for PID and without PID, respectively. After adjustment for confounders, age of less than 50 years, the presence of diabetes mellitus, and PID were significantly positivity associated with the risk of second primary cancers. The hazard ratios (HRs) of age less than 50 years, diabetes mellitus, and PID were 1.38 (95% CI = 1.11-2.04), 1.40 (95% CI = 1.06-1.85), and 1.35 (95% CI = 1.00-1.81), respectively. A higher incidence of second primary cancers was observed in the genitals, bladder, and colon.In conclusion, the incidence of second primary cancers was higher in the genitals, bladder, and colon in patients with cervical cancer treated with surgery alone. The patients with PID had a higher risk of second primary cancers.

Implementing web-based ping-pong-type e-communication to enhance staff satisfaction, multidisciplinary cooperation, and clinical effectiveness: A SQUIRE-compliant quality-improving study.

BACKGROUND: Frequent multidisciplinary communication is essential in conducting daily radiotherapy (RT) practice. However, traditional oral or paper-based communication has limitations. E-communication has been suggested, but its effects are still not well demarcated in the field of radiation oncology. OBJECTS: In our web-based integrated information platform, we constructed a ping-pong-type e-communication function to transfer specific notations among multidisciplinary RT staffs. The purpose was to test whether applying this e-communication can increase effectiveness of multidisciplinary cooperation when compared with oral or paper-based practice. Staff satisfaction and clinical benefits were also demonstrated. DESIGN AND SETTING: A real-world quality-improving study was conducted in a large center of radiation oncology. PARTICIPANTS AND DATASET USED: Before and after applying multidisciplinary e-communication (from 2014 to 2015), clinical RT staffs were surveyed for their user experience and satisfaction (n = 23). For measuring clinical effectiveness, a secondary database of irradiated head and neck cancer patients was re-analyzed for comparing RT toxicities (n = 402). INTERVENTIONS: Applying ping-pong-type multidisciplinary reflective e-communication was the main intervention. OUTCOME MEASURES: For measuring staff satisfaction, eight domains were surveyed, such as timeliness, convenience, and completeness. For measuring clinical effectiveness of multidisciplinary cooperation, event rates of severe (i.e., grade 3-4) RT mucositis and dermatitis were recorded. RESULTS: Overall, when compared with oral communication only, e-communication demonstrated multiple benefits, particularly on notation-review convenience (2.00 ±â€Š1.76 vs 9.19 ±â€Š0.81; P < 0.0001).When compared with paper-based practice, e-communication showed statistically significant benefits on all eight domains, especially on notation-review convenience (5.05 ±â€Š2.11 vs 9.19 ±â€Š0.81; P < 0.0001) and convenience of feedback notation (4.81 ±â€Š1.72 vs 8.76 ±â€Š1.09; P < 0.0001).Moreover, staff satisfaction was gradually increased from oral (3.57 ±â€Š1.94), paper-based (5.57 ±â€Š2.06), to e-communication (8.76 ±â€Š0.70; P < 0.0001). Secondary measurement confirmed these observations.Before and after facilitating multidisciplinary cooperation by using e-communication, severe (i.e., grade 3-4) mucositis and dermatitis were decreased from 21.7% to 10% then to 5.1%. CONCLUSIONS: Replacing oral or paper-based practice with e-communication is useful in facilitating RT multidisciplinary teamwork. Staff satisfaction and clinical effectiveness can be increased.

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma: A care-compliant case report.

BACKGROUND: Clinically, elderly patients with unresectable bulky hepatocellular carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor control were observed. CASE SUMMARY: At presentation, an 85-year-old male patient complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a 12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA (cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA), trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEB-VMAT technique was given alternatively. RT was delivered in 26 fractions, with dose gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized potential anti-HCC agent) was retrospectively found to be prescribed for alleviating skin itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for 24 months).After RT, significant symptoms alleviation and tumor volume reduction were observed for 32 months till multiple bone metastases. Before and after RT, a large tumor volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe treatment toxicity was noted during and after RT. The patient died due to aspiration pneumonia with septic shock at 4 months after bone metastases identified. CONCLUSIONS: SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were observed in this elderly patient with unresectable bulky HCC. Further prospective randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without cyproheptadine.

Leukemia Risk After Cardiac Fluoroscopic Interventions Stratified by Procedure Number, Exposure Latent Time, and Sex: A Nationwide Population-Based Case-Control Study.

A number of cardiac fluoroscopic interventions have increased rapidly worldwide over the past decade. Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation have become increasingly popular, and these advancements have allowed patients to receive repetitive treatments for restenosis. However, these advancements also significantly increase radiation exposure that may lead to higher cumulative doses of radiation. In the present study, a nationwide population-based case-controlled study was used to explore the risk of leukemia after cardiac angiographic fluoroscopic intervention.A total of 5026 patients with leukemia and 100,520 control patients matched for age and sex (1:20) by a propensity score method without any cancer history were enrolled using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan between 2008 and 2010. All subjects were retrospectively surveyed (from year 2000) to determine receipt of cardiac fluoroscopic interventions. Data were analyzed using conditional logistic regression models, and estimated crude and adjusted odds ratios (95% confidence interval).After adjusting for age, gender, and comorbidities, PTCA was found to be associated with an increased risk of leukemia with an adjusted OR of 1.566 (95% CI, 1.282-1.912), whereas coronary angiography alone without PTCA and cardiac electrophysiologic study were not. Our results also showed that an increased frequency of PTCA and coronary angiography was associated with a higher risk of leukemia (adjusted OR: 1.326 to 1.530 [all P < 0.05]). Gender subgroup analyses demonstrated that men were associated with a higher risk of leukemia compared with women.These results provide additional data in the quantification of the long-term health effects of radiation exposure derived from the cardiac fluoroscopic diagnostic and therapeutic intervention. PTCA alone or PTCA with coronary angiography was associated with an elevated risk of leukemia. Continued follow-up of existing cohorts will be valuable to help assess lifetime risks of cancer.

Effect of 23-Valent Pneumococcal Polysaccharide Vaccine Inoculated During Anti-Cancer Treatment Period in Elderly Lung Cancer Patients on Community-Acquired Pneumonia Hospitalization: A Nationwide Population-Based Cohort Study.

To evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined "vaccination period," first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence.This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during "vaccination period", and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were ≥75 years old and still survival post "vaccination period." Incidence density (ID) of all-cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan-Meier method, respectively.After a 4-year follow-up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR] = 0.740, P = 0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both P < 0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP.For elderly lung cancer patients aged ≥75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival.

Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study.

OBJECTIVE: The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis. METHODS: This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated. RESULTS: The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03). CONCLUSIONS: Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis.

Vascular invasion affects survival in early hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with a high mortality rate. The optimal therapeutic choice for early HCC is surgical resection. However, the rate of intrahepatic recurrence is high. The objective of this study was to evaluate the effect of various factors on the survival of patients with early HCC. Between January 1st, 2006 and December 31st, 2013, a total of 89 patients who underwent surgery for HCC were retrospectively enrolled. The analysis was conducted using the Student's t-test, Chi-square test, Kaplan-Meier method and Cox proportional hazard regression model to assess potential confounding and predictive variables. The 3-year overall survival (OS) rate was 71%. The 3-year OS rates in patients with and those without vascular invasion were 62.1 and 92.8%, respectively (P<0.003). Based on the multivariate analysis, postoperative pathological vascular invasion (hazard ratio = 4.96; 95% confidence interval: 1.55-15.9) remained an independent predictor of adverse long-term outcome. Furthermore, vascular invasion was significantly associated with intrahepatic metastasis. These data emphasize the need for effective adjuvant therapy in selected high-risk patients with early HCC. Further studies are required to determine the optimal approach to further improving the prognosis of early HCC.

DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study.

Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation.

Use of Chinese medicine among colorectal cancer patients: a nationwide population-based study.

BACKGROUND: Traditional Chinese medicine (CM) appears to be used worldwide, especially by cancer patients. The aim of the present study was to explore CM uses and CM non-users by patients with colorectal cancer (CRC). MATERIALS AND METHODS: A retrospective study was conducted using registration and claims data sets for 2007 from the National Health Insurance Research Database. Patients with colorectal cancer were identified from the Registry for Catastrophic illness Patients. Binary logistic regression was used to estimate odds ratios as the measure of association with the use of CM. RESULTS: A total of 61,211 CRC patients diagnosed in 2007 were analysis. Most CM users preferred to visit private clinics (46.9%) with 306,599 visits. In contrast, the majority of CM non-users preferred to visit private hospitals (42.2%) with 538,769 visits. Among all 176,707 cancer-specific CM visit, there were 66.6% visits to CM outpatient department (OPD) of private hospitals, while in 477,612 non-cancer-specific CM visits, 62.0% was for private clinics. The proportion of expenses for diagnostic fees for CM user in CM visits was much less than that for WM visits and CM non-users (US$4.6 vs. 29.3 vs. 33.5). The average cost for CM user in CM was less than that for WM visits and CM non-users (US$6.3 vs. 25.9 vs. 30.3). Female patients, younger age, and patients not living in the northern region, with higher EC or more comorbidities were more likely to receive CM treatment. CONCLUSION: The prevalence and costs of insurance-covered CM among CRC patients were low. Further longer longitudinal study is needed to follow up this trend.

Higher caseload improves cervical cancer survival in patients treated with brachytherapy.

OBJECTIVES: Increased 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. METHODS: Between 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. RESULTS: As 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). CONCLUSIONS: Provider 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 (n = 112) and surgery-alone (n = 448). 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%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44-12.22; P = 0.009). 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.