Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

The 2017 Women's Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study.

BACKGROUND: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. METHODS: We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. RESULTS: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. CONCLUSIONS: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

Impact of Weekend Effect on Short- and Long-Term Survival of Patients Undergoing Esophagectomy for Cancer: A Population-Based, Inverse Probability of Treatment-Weighted Analysis.

BACKGROUND: We examined the impact of the weekend effect on the survival outcomes of patients undergoing elective esophagectomy for cancer. METHODS: This was a retrospective analysis of a nationwide, health administrative dataset that included all patients (n = 3235) who had undergone elective esophagectomy for cancer in Taiwanese hospitals between 2008 and 2015. Patients were categorized according to the day of surgery (weekday group: surgical procedures starting Monday through Friday, n = 3148; weekend group: surgical procedures starting on Saturday or Sunday, n = 87). Inverse probability of treatment weighting (IPTW) using the propensity score was used to account for selection bias due to baseline differences. RESULTS: After IPTW, patients undergoing esophagectomy on weekends had a higher 90-days mortality rate compared with those undergoing surgery on a weekday (10.5% vs. 5.5%, respectively, P < 0.001). After controlling for potential confounders, weekend surgery was identified as an independent adverse predictor of 2-years, overall survival [hazard ratio (HR) = 1.38, P < 0.001]. Importantly, inferior weekend outcomes were especially evident in certain subgroups, including patients aged > 60 years (HR = 1.61, P < 0.001), as well as those with a high burden of comorbidities (HR = 1.32, P < 0.001), advanced tumor stage (HR = 1.50, P < 0.001), histological diagnosis of squamous cell carcinoma (HR = 1.20, P < 0.001), and treated with minimally invasive esophagectomy (HR = 1.26, P < 0.001). CONCLUSIONS: Elective esophagectomy for cancer during weekends has an adverse impact on short- and long-term survival.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

Treatment burden and cost-effectiveness analysis of the neoadjuvant CROSS regimen in esophageal squamous cell carcinoma: a multicenter retrospective study.

High-quality evidence indicated that both neoadjuvant carboplatin/paclitaxel (CROSS) and cisplatin/5-fluorouracil (PF) regimens in combination with radiotherapy improve survival outcomes compared to surgery alone in patients with esophageal cancer. It is not yet known whether they may differ in terms of treatment burden and healthcare costs. A total of 232 Taiwanese patients with esophageal squamous cell carcinoma who had undergone neoadjuvant chemoradiotherapy (nCRT) with either the CROSS (n = 153) or the PF (n = 79) regimens were included. Hospital encounters and adverse events were assessed for determining treatment burden. Cost-effectiveness analysis was undertaken using the total costs incurred over 3 years in relation to overall survival (OS) and progression-free survival (PFS). Compared with PF, the CROSS regimen was associated with a lower treatment burden: shorter inpatient days on average (4.65 ± 10.05 vs. 15.14 ± 17.63 days; P < 0.001) and fewer admission requirements (70% of the patients were never admitted vs. 20% in the PF group; P < 0.001). Patients in the CROSS group experienced significantly less nausea, vomiting, and diarrhea. While the benefits observed in the CROSS group were associated with additional nCRT-related expenditures (1388 United States dollars [USD] of added cost per patient), this regimen remained cost-effective. At a willingness-to-pay threshold of 50,000 USD per life-year, the probability of the CROSS regimen to be more cost-effective than PF was 94.1% for PFS but decreased to 68.9% for OS. The use of the CROSS regimen for nCRT in patients with ESCC was associated with a lower treatment burden and was more cost-effective than PF.

Neoadjuvant Therapy Versus Upfront Surgery for Patients With Clinical Stage 2 or 3 Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

BACKGROUND: Although neoadjuvant therapy followed by surgery (NT) is the standard of care for esophageal cancer in Western countries, upfront surgery (US) followed by adjuvant therapy (when indicated) still is commonly used in Asia to minimize overtreatment. This study investigated the cost-effectiveness of NT versus US for patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients with a diagnosis of ESCC between 2010 and 2015 were divided into NT or US according to the intention to treat. Two propensity score-matched groups of patients with clinical stage 2 (135 pairs) or stage 3 (194 pairs) disease were identified and compared in terms of overall survival (OS) and direct costs incurred within 3 years after diagnosis. RESULTS: The esophagectomy rates after NT were 82% for stage 2 and 88% for stage 3 disease. Compared with US, surgery after NT was associated with higher R0 resection rates, a lower number of dissected lymph nodes, and similar postoperative mortality. On an intention-to-treat analysis, stage 3 patients who received NT had a significantly better 3-year OS rate (45%) than those treated with US (37%) (p = 0.029) without significant cost increases (p = 0.89). However, NT for clinical stage 2 disease neither increased costs nor improved 3-year OS rates (47% vs 47%; p = 0.88). At a willingness-to-pay level of US$50,000 per life-year, the probability of NT being cost-effective was 92% for stage 3 versus 59% for stage 2 ESCC. CONCLUSION: Because of its higher cost-effectiveness, NT is preferable to US for patients with clinical stage 3 ESCC, but US remains a viable option for stage 2 disease.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Duration of varenicline prescription and efficacy of smoking cessation treatment: an observational study in Taiwan.

Although varenicline has had a significant effect on smoking cessation in randomized clinical trials, the dose-effect of varenicline treatment for smoking cessation in real-world settings remains unclear. This study aimed to evaluate the association between the duration of varenicline prescription and smoking cessation in Taiwan after adjusting for potential confounding effects and endogeneity bias. A total of 5106 Taiwanese participants received varenicline monotherapy for smoking cessation between March 2012 and September 2016. Multinomial logistic regression (MLR) was used to analyze the association between varenicline prescription duration and smoking cessation, stratified by the frequency of smoking clinic visits and propensity scores of early stopping of smoking cessation treatment. Compared to the reference of nonquitting, longer durations of varenicline prescription were associated with the greater likelihood of immediate and complete quitting (OR = 1.08, 95% CI = 1.02-1.14) and late quitting (OR = 1.14, 95% CI = 1.07-1.20). Among those who were more likely to continue visiting smoking clinics, longer use of varenicline was significantly associated with an increase in immediate-and-complete quitting (OR = 1.19, 95% CI = 1.15-1.23) and late quitting (OR = 1.24, 95% CI = 1.20-1.28). Varenicline prescription duration was not associated with smoking cessation among smokers who visited smoking clinics once. The relationship between varenicline prescription duration and smoking cessation was modified by the frequency of smoking clinic visits and was dependent on quitting process patterns. Encouraging smokers to continue visiting the smoking cessation clinic and use medication will help smoking cessation efforts in Taiwan.

Predicting the risk of interval distant metastases in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy.

BACKGROUND: This study was conducted to identify risk factors for distant interval metastases (IM) in patients with esophageal squamous cell carcinoma (ESCC) who underwent chemoradiotherapy (CRT). METHODS: We retrospectively reviewed the clinical records of 358 patients with ESCC treated with CRT between 2006 and 2017. Distant IM were defined as systemic metastases developing during or shortly after CRT and identified during the restaging work-up period. A risk prediction nomogram for distant IM was developed based on independent pretreatment risk factors identified using multivariable logistic regression analysis. RESULTS: Distant IM occurred in 26 (7.3%) patients and had a significant adverse impact on survival (median survival: 8.7 months). The most common site of distant IM was the lung (n = 9), followed by non-regional lymph nodes (n = 8) and the bone (n = 8). Multivariable logistic regression analysis revealed that high baseline tumor SUVmax values were independently associated with an increased risk of distant IM (odds ratio [OR] = 1.059, p = 0.019), whereas older age was an independent protective factor (OR = 0.946, p = 0.032). A nomogram based on age, tumor SUVmax, tumor length, and the chemotherapy regimen showed a good predictive performance (c-statistic = 0.761), which was internally validated using 200 bias-corrected bootstrap replicates (c-statistic = 0.71). CONCLUSION: Distant IM were identified in 7.3% of patients with ESCC undergoing CRT. The nomogram described in our study may prove useful to predict the risk of distant IM in this patient group.

Cost-effectiveness analysis of thoracoscopic versus open esophagectomy for esophageal cancer: a population-based study.

The question as to whether the clinical benefits of video-assisted thoracoscopic esophagectomy (VATE) do outweigh its increased costs remains unanswered. Here, we analyzed the cost-effectiveness of VATE versus open esophagectomy (OE) in a real-world setting. Using 2008-2015 Taiwanese Health Insurance claim data, we identified 3271 patients with esophageal cancer who underwent transthoracic esophagectomy. By taking into account nine confounding variables, we constructed a 1:1 propensity score-matched sample of patients who underwent VATE or OE (n = 629 each). Direct costs incurred within three years after surgery and survival were analyzed. There were no significant intergroup differences in terms of R0 resection rates, length of stay, as well as 30- and 90-day mortality and unplanned readmission rates. However, the number of dissected nodes was higher in the VATE group (median: 24 vs. 18, P < 0.001). While VATE had higher index hospitalization costs (median, 12331 USD vs. 10730 USD, P < 0.001), cost differences were reduced over time. The average accumulated cost person-month of VATE declined below that of OE at 14 months after hospital discharge. Overall survival (OS) figures were more favorable for patients treated with VATE (3-year OS: 47% vs. 41%; life expectancy: 4.04 life-years [LY] vs. 3.30 LY). The cost-effectiveness plane showed that only 0.3% of all VATE procedures were more costly and less effective than OE. The probabilities for VATE to be cost-effective at the willingness-to-pay (WTP) thresholds of 10000 and 50000 USD/LY were 63.5% and 92.4%, respectively. Using commonly accepted WTP thresholds, VATE was more cost-effective than OE for patients with esophageal cancer.

Transition from video-assisted thoracoscopic to robotic esophagectomy: a single surgeon's experience.

Lymph node dissection (LND) along the left recurrent laryngeal nerve (RLN) is a technically challenging part of esophageal cancer surgery, especially after chemoradiotherapy (CRT). Robotic surgery holds promise to increase its safety and feasibility. The aim of this study was to describe a single thoracoscopic surgeon's experience related to the transition from video-assisted esophagectomy (VATE) to robotic esophagectomy (RE)-with a special focus on the safety of left RLN LND. Patients who underwent minimally invasive esophagectomy and RLN dissection following CRT were dichotomized according to the use of robotic surgery (robotic esophagectomy [RE] versus video-assisted thoracoscopic esophagectomy [VATE]). The following parameters were determined: (1) number of dissected nodes, (2) rates of RLN palsy, (3) rates of perioperative complications, and (4) learning curve. Learning curve analysis was performed using the 10-patient moving average (MA) for operation times and with the cumulative sum (CUSUM) method for left RLN LND (target failure rate: 15%). The RE and VATE groups consisted of 39 and 67 patients, respectively. The intraoperative identification of the left RLN was more common in the RE group (97.4%) than in the VATE group (68.7%; P < 0.001). Postoperative left RLN palsy was significantly more frequent in the VATE group (26.9%) than in the RE group (10.3%; P = 0.042), with a higher rate of pneumonia in the former (16.4% versus 2.6%; P = 0.03). The MA chart revealed a downward trend followed by a flattening of the RE operation time at operation number 17 and 29, respectively. CUSUM analysis showed that the left RLN palsy rate decreased to the target rate after 12 operations. We conclude that at least 12 cases are required for a surgeon with prior experience in VATE to safely accomplish left RLN LND through a robotic approach.

Incidence and Predictors of Unsuspected Recurrent Laryngeal Nerve Lymph Node Metastases After Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Radical lymph node (LN) dissection along the recurrent laryngeal nerve (RLN) area carries a substantial morbidity rate, and its usefulness in neoadjuvant chemoradiotherapy (nCRT)-treated esophageal cancer patients remains unclear. METHODS: This study was conducted in two Asian thoracic surgery centers. Patients with esophageal squamous cell carcinoma (ESCC) who were judged to be ycN-RLN(-) after nCRT and received bilateral RLN LN dissection were eligible. The incidence of unsuspected RLN LN involvement was analyzed, and we used least absolute shrinkage and selection operator (LASSO) regression to identify its predictors. RESULTS: A total of 56 patients (53 males and 3 females; mean age: 55 years) were included. The upper mediastinum-including the bilateral RLN area-was covered by the radiation field in 48 (85.3%) patients. Although all of them were judged as ycN-RLN(-), unsuspected RLN LN involvement was identified on pathological examination in 11 (19.6%) subjects, being the only positive nodal station in seven. LASSO regression identified the pre-nCRT RLN LN(cN-RLN) status as the only independent predictor of ypN-RLN positivity; in contrast, neither the tumor location nor the radiation dose to the upper mediastinum were independently associated with ypN-RLN(+). RLN nodal dissection resulted in positive LN discovery rates of 30.8 and 10% in ycN-RLN(-) patients who had positive and negative cN-RLNs before nCRT, respectively. Consequently, 23.1 and 6.7% of patients in each subgroup would have been understaged in the absence of RLN nodal dissection. CONCLUSION: Nearly one-fifth of ESCC patients who were judged to be ycN-RLN(-) unexpectedly had positive ypN-RLN. The pre-nCRT cN-RLN status plays a key role in the selection of patients that should undergo RLN LN dissection after nCRT.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Comparative Associations Between Measures of Anti-cholinergic Burden and Adverse Clinical Outcomes.

PURPOSE: No consensus has been reached regarding which anticholinergic scoring system works most effectively in clinical settings. The aim of this population-based cohort study was to examine the association between anticholinergic medication burden, as defined by different scales, and adverse clinical outcomes among older adults. METHODS: From Taiwan's Longitudinal Health Insurance Database, we retrieved data on monthly anticholinergic drug use measured by the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden Scale (ACB), and the Drug Burden Index - Anticholinergic component (DBI-Ach) for 116,043 people aged 65 years and older during a 10-year follow-up. For all 3 scales, a higher score indicates greater anticholinergic burden. We used generalized estimating equations to examine the association between anticholinergic burden (ARS and ACB: grouped from 0 to ≥4; DBI-Ach: grouped as 0, 0-0.5, and 0.5-1) and adverse outcomes, and stratified individuals by age-group (aged 65-74, 75-84, and ≥85 years). RESULTS: Compared with the ARS and DBI-Ach, the ACB showed the strongest, most consistent dose-response relationships with risks of all 4 adverse outcomes, particularly in people aged 65 to 84 years. For example, among those 65 to 74 years old, going from an ACB score of 1 to a score of 4 or greater, individuals' adjusted odds ratio increased from 1.41 to 2.25 for emergency department visits; from 1.32 to 1.92 for all-cause hospitalizations; from 1.10 to 1.71 for fracture-specific hospitalizations; and from 3.13 to 10.01 for incident dementia. CONCLUSIONS: Compared with the 2 other scales studied, the ACB shows good dose-response relationships between anticholinergic burden and a variety of adverse outcomes in older adults. For primary care and geriatrics clinicians, the ACB may be a helpful tool for identifying high-risk populations for interventions.

Unexpected Microscopically Positive Proximal Resection Margins in Esophageal Squamous Cell Carcinoma After Chemoradiotherapy: Predictors and Prognostic Significance.

BACKGROUND: Esophageal cancer has the propensity to spread in a longitudinal manner (either proximally or distally), potentially resulting in the unexpected presence of microscopic disease at grossly tumor-free margins. The clinical significance of this phenomenon in patients treated with chemoradiotherapy (CRT) remains unclear. The purpose of this study was to investigate the prevalence, predictors, and prognostic impact of microscopically positive proximal resection margins (PPRMs) in patients with esophageal squamous cell carcinoma (ESCC) who received CRT. METHODS: Between 2000 and 2014, we identified 332 ESCC patients who underwent complete gross resection (R0/R1) following CRT. Patients were divided into two groups according to the status of the proximal resection margins on microscopic examination [negative proximal resection margins (NPRMs) vs PPRMs]. The occurrence of anastomotic leakage (AL) and anastomotic recurrence (AR) served as outcome measures. RESULTS: Sixteen (4.8 %) patients had PPRM. The presence of PPRM was not associated with AL but was a strong predictor of AR (PPRM vs NPRM, 23.1 vs 7 %, respectively, P = 0.033). Multivariate analysis identified a resection margin length <3.5 cm [odds ratio (OR) 4.473, P = 0.022] and salvage resection (OR 3.171, P = 0.045) as independent predictors of PPRM. The estimated PPRM rates were 16.7, 6.3, and 1.3 % for patients with 2, 1, and 0 predictors, respectively. CONCLUSIONS: PPRM occurred in 4.8 % of ESCC patients following CRT and was associated with AR. An intraoperative frozen section margin analysis should be performed in patients carrying risk factors to avoid unexpected PPRM.

Development of a nomogram for the prediction of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Nomograms incorporating multiple prognostic factors are useful for individualized estimation of survival in cancer patients. However, nomograms for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer are scarce. Here, we describe the development of a nomogram for predicting pCR after nCRT in patients with esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed the records of 392 ESCC patients who underwent nCRT followed by esophagectomy. Seventy percent of the participants (n = 274) were randomly assigned to a training cohort, whereas the remaining 30% were included in a validation cohort (n = 118). Data from the training cohort were subjected to multivariate logistic regression analyses for selecting variables to be included in the nomogram. The performance of the resulting nomogram was internally and externally validated by calculating the bias-corrected concordance statistic (c-statistic) and the area under the receiver operating characteristics curve (AUROC) in the training and validation cohorts, respectively. After surgery, 25.77% of the study patients achieved pCR. The following variables were included in the nomogram: (i) age, (ii) pretreatment tumor length, (iii) history of head and neck cancer, (iv) post-nCRT albumin levels, and (v) post-nCRT endoscopic findings coupled with endoscopic biopsy results. The bias-corrected c-statistic and AUROC of the internal and external validation sets were 0.77 and 0.747, respectively. Our nomogram showed a good performance for predicting pCR after nCRT in ESCC patients.

To Load or Not to Load? Aspirin Loading in Acute Ischemic Stroke: A Study of Clinical Outcomes.

BACKGROUND AND PURPOSE: Aspirin is known to reduce mortality and recurrent vascular events. However, there are no reports about the dose-response of loading aspirin in treating acute ischemic stroke. The objective of this study was to compare the effectiveness of different loading doses of aspirin in acute ischemic stroke presenting within 48 hours of symptom onset. METHODS: This was a retrospective, hospital-based cohort study. Patients were classified as high dose (160-325 mg) or low dose (<160 mg) based on the initial loading dose of aspirin at the emergency department. The primary outcome measure was a favorable modified Rankin Scale (mRS) score of 1 or lower on discharge. Secondary outcomes included in-hospital mortality, stroke progression during admission, and bleeding events. A propensity score with 1:3 matching was used to balance baseline characteristics, and stepwise multiple logistic regression was performed for variable adjustment. RESULTS: From a total of 7738 available patients, 3802 patients were included. Among them, 750 patients were in the high-dose group. Multiple logistic regression after matching revealed that the high-dose group was significantly associated with a favorable clinical outcome on discharge (odds ratio: 1.49, 95% confidence interval: 1.17-1.89, P <.01), but not mortality or stroke progression. The high-dose group also experienced more minor bleeding events. CONCLUSIONS: A higher loading dose of aspirin (160-325 mg) can be beneficial in treating acute ischemic stroke, although there is an increased risk of minor bleeding.

Epidemiology, clinical profile and treatment patterns of venous thromboembolism in cancer patients in Taiwan: a population-based study.

BACKGROUND: Venous thromboembolism (VTE) is a clinically significant complication that is well documented among Caucasian cancer patients. However, evidence regarding VTE incidence and treatment among Asian cancer patients is very limited. The objective of this study is to investigate the incidence, risk factors and management of VTE among Taiwanese cancer patients. METHODS: Using Taiwan's National Health Insurance Research Database, we identified 43,855 newly diagnosed cancer patients between 2001 and 2008. Two alternative algorithms for identifying VTE event were explored to better quantify a range of incidence rates of VTE in our cancer patients. Multivariable logistic regression models were used to explore VTE risk factors. RESULTS: The incidence rates of VTE were 9.9 (algorithm 1) and 3.4 (algorithm 2) per 1,000 person-years, respectively. The incidence rates were higher in certain cancers, particularly liver, pancreas, and lung. Significant risk factors for VTE were site of cancer, prior history of VTE, chemotherapy and major surgeries. Long-term anticoagulant therapy was initiated in 64.1% patients with VTE and 72.2% of them received warfarin alone. Approximately two-thirds of patients with VTE received ≤ 3 months of anticoagulant therapy. CONCLUSION: Incidence of cancer-related VTE is lower among Taiwanese compared to Caucasian populations. Nevertheless, risk factors for cancer-related VTE found in our study were consistent with current literature.

Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study.

BACKGROUND: Polypharmacy, potentially inappropriate medications and anticholinergic burden (as assessed by the anticholinergic risk scale) are commonly used as quality indicators of pharmacotherapy in older adults. However, their role in clinical practice is undefined. We sought to investigate longitudinal changes in these indicators and their effects on clinical outcomes. METHODS: We used Taiwan's Longitudinal Health Insurance Database to retrieve quarterly information about drug use for people aged 65 years and older over a 10-year period. We analyzed the association between indicators and all-cause admission to hospital, fracture-specific admission to hospital and death using generalized estimating equations. RESULTS: The study cohort comprised 59,042 older adults (65-74 yr: 39,358 [66.7%], 75-84 yr: 16,903 [28.6%], and ≥ 85 yr: 2781 [4.7%]). The mean changes in polypharmacy over the course of the study were greatest among patients aged 65-74 years (absolute difference +2.14, 95% confidence interval [CI] 2.10-2.19), then among those aged 75-84 yr (+1.79, 95% CI 1.70-1.88), and finally those aged 85 years and older (+0.71, 95% CI 0.36-1.05). The number of potentially inappropriate medications increased among patients aged 65-74 years (+0.16 [0.15-0.18]) and 75-84 years (+0.09 [0.06-0.08]), but decreased in those aged 85 years and older (-0.15 [-0.26 to -0.04]). Polypharmacy, potentially inappropriate medications and anticholinergic risk scale were each associated with an increased risk of admission to hospital, but not with death. In addition, both polypharmacy (5-9 drugs: odds ratio [OR] 1.18, 95% CI 1.12-1.24; ≥ 10 drugs: OR 1.54, 95% CI 1.42-1.66) and anticholinergic burden (score 1-2: 1.39, 95% CI 1.31-1.48; ≥ 3: 1.53, 95% CI 1.41-1.66) showed dose-response relations with fracture-specific admission to hospital. INTERPRETATION: The total number of drugs taken (polypharmacy), number of potentially inappropriate medications and anticholinergic risk changed during follow-up and varied across age groups in this cohort of older adult patients. These indicators showed dose-response relations with admission to hospital, but not with death.