Clinical and Dosimetric Results of Proton or Photon Radiation Therapy for Large (>5 cm) Hepatocellular Carcinoma: A Retrospective Analysis.

PURPOSE: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy. METHODS AND MATERIALS: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison. RESULTS: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 Gy exhibited significantly better local control (LC; 2-year: 85.6% vs 20.5%; P < .001), progression-free survival (PFS; median, 7.4 vs 3.2 months; P < .001), and overall survival (OS; median, 18.1 vs 7.3 months; P < .001) compared with those with BED10 < 75 Gy. Notably, proton-treated patients had a significantly higher BED10 (96 vs 67 Gy; P < .001) and improved LC (2-year: 88.5% vs 33.8%; P < .001), PFS (median, 7.4 vs 3.3 months; P = .001), and OS (median, 18.9 vs 8.3 months; P < .001) than those undergoing photon radiation therapy. Furthermore, patients treated with protons had significantly lower V1 of the liver (P < .001), mean upper gastrointestinal tract dose (P < .001), and mean splenic dose (P < .001), with significantly decreased incidences of radiation-induced liver disease (P = .007), grade ≥3 upper gastrointestinal bleeding (P = .001), and grade ≥3 lymphopenia (P = .003). On multivariate analysis, proton radiation therapy consistently correlated with superior LC (P < .001), PFS (P < .001), and OS (P < .001). In intragroup dosimetric comparison, photon plans demonstrated significantly higher mean liver dose (P < .001) compared with actually delivered proton treatments, and 72 (69%) of them had mean liver dose exceeding 28 Gy, which necessitated target dose de-escalation. CONCLUSIONS: In the context of large HCC radiation therapy, a higher target BED10 was associated with improved outcomes. Notably, proton therapy has demonstrated the capability to deliver ablative doses while also being accompanied by fewer instances of severe toxicity.

Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.

Efficacy of Postoperative Unilateral Neck Irradiation in Patients with Buccal Mucosa Squamous Carcinoma with Extranodal Extension: A Propensity Score Analysis.

Unilateral radiotherapy (RT) as a postoperative treatment for multiple ipsilateral lymph node (LN) metastases remains controversial. We investigated the efficacy of postoperative unilateral RT for buccal mucosa squamous cell carcinoma (BMSCC) with extranodal extensions (ENEs). We retrospectively reviewed the clinical records of 186 patients with ENE+ BMSCC who received postoperative RT during 1997-2016. Propensity score matching was used to establish comparable cohorts. The endpoints were contralateral nodal control (CLNC), overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), local control (LC), and regional control (RC). After matching, 123 patients were selected for analysis; 45 (36.6%) and 78 (63.4%) patients underwent unilateral and bilateral RT, respectively. The median follow-up was 36.27 months. The survival outcomes in the unilateral and bilateral RT groups were similar: 3-year CLNC (85.6% vs. 89.1%, p = 0.748), OS (53.2% vs. 57.4%, p = 0.229), DFS (46.5% vs. 48.6%, p = 0.515), DMFS (70.7% vs. 72.0%, p = 0.499), LC (78.0% vs. 75.6%, p = 0.692), and RC (79.9% vs. 76.2%, p = 0.465). On multivariable Cox regression analysis, unilateral and bilateral RT showed comparable outcomes; the number of ENEs ≥ 4 was the only significant prognostic factor for all clinical outcomes. Using decision tree analysis, we classified our patients to have a low, intermediate, or high risk of contralateral failure based on three factors: number of ENEs, margin status, and tumor stage. In conclusion, postoperative unilateral RT did not worsen outcomes in patients with ENE+ BMSCC in this cohort. The decision tree model may assist physicians in optimizing and tailoring radiation fields.

Comparative prognostic value of different preoperative complete blood count cell ratios in patients with oral cavity cancer treated with surgery and postoperative radiotherapy.

BACKGROUND: We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). METHODS: We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. RESULTS: The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656-0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478-0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high-risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p < 0.03)-with a borderline significance being evident for DC in patients with T4 disease (p = 0.058). CONCLUSIONS: A high pretreatment NLR was an independent unfavorable risk factor for both OS and DC in patients with OSCC who underwent surgery and PORT. No other preoperative complete blood count parameters and cell ratios were found to have prognostic significance.

Prognostic value of radiologic extranodal extension in patients with hypopharyngeal cancer treated with primary chemoradiation.

BACKGROUND AND PURPOSE: We aimed to evaluate the prognostic value of radiologic extranodal extension (rENE) in patients with hypopharyngeal cancer (HPC) treated with primary chemoradiation. MATERIALS AND METHODS: Cancer registry data were reviewed from 2005 to 2014. Inclusion criteria included HPC, clinical N1-3 disease (AJCC staging system, 7th edition), and receiving radiotherapy. Patients with M1 diseaseor with synchronous/metachronous cancer were excluded. Staging images were reviewed by two radiologists. rENE was defined as infiltration of adjacent fat/muscles, irregular nodal surface, or irregular capsular enhancement. Clinical stage, rENE status, and clinical outcome were analyzed. RESULTS: Overall, 355 patients were included. Patients with rENE had lower 3-year overall survival (OS) and recurrence-free survival (RFS) rates. Univariate analysis showed that clinical T4 or N3 stage, overall stage IV, and rENE correlated with OS and RFS. In multivariate analysis, clinical T4 or N3 stage correlated with poor OS, while clinical T4 or N3 stage and rENE were independent predictors of poor RFS. N1/2 without rENE was designated as Group 1, N1/2 with rENE as Group 2, and N3 with/without rENE as Group 3. The 3-year RFS rates in Groups 1, 2, and 3 were 55.8%, 41.0%, and 29.3%, respectively. The 3-year RFS rate in Group 1 was significantly higher than that in the other two groups. CONCLUSIONS: rENE is an adverse prognostic factor for survival in patients with HPC treated with primary chemoradiation. It correlated with inferior RFS regardless of N stage. rENE may be used as a criterion for clinical ENE in future staging systems.

Prognostic significance of the preoperative systemic immune-inflammation index in patients with oral cavity squamous cell carcinoma treated with curative surgery and adjuvant therapy.

OBJECTIVES: To investigate the prognostic value of the preoperative systemic immune-inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC-SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients with OC-SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden's index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC). RESULTS: The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p < 0.001). No independent association between SII and LC/RC was observed. CONCLUSION: Increased SII values predict poor DC and OS in patients with OC-SCC treated with curative resection and adjuvant RT/CCRT. Owing to the higher risk of systemic failure in this patient group, a thorough follow-up surveillance schedule may be advisable pending independent confirmation of our data.

Prognostic significance of dynamic changes in lymphocyte-to-monocyte ratio in patients with head and neck cancer treated with radiotherapy: results from a large cohort study.

BACKGROUND AND PURPOSE: We sought to investigate whether dynamic changes in lymphocyte-to-monocyte ratio (LMR) occurring during the course of radiotherapy (RT) may have prognostic value in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients with HNC who underwent RT at our center between 2005 and 2013. Generalized estimating equations were used to longitudinally assess changes in LMR through the course of RT. Delta-LMR was calculated as the difference between LMR measured during treatment and baseline LMR values. Freedom from metastasis (FFM) and overall survival (OS) served as the main outcome measures. RESULTS: A total of 1431 patients with HNC were enrolled. After a median follow-up of 9 years, 636 (44.4%) patients died and 240 (16.8%) had distant metastases. Compared with patients with low delta-LMR at two weeks, those with high delta-LMR experienced less favorable outcomes (five-year OS: 73% versus 59%, respectively, p < 0.001; five-year FFM: 87% versus 80%, respectively, p = 0.015). Similar findings were observed for delta-LMR measured at four weeks (five-year OS: 72% versus 60%, p < 0.001; five-year FFM: 86% versus 79%, respectively, p = 0.002) and six weeks (five-year OS: 72% versus 57%, p < 0.001; five-year FFM: 87% versus 79%, respectively, p = 0.002). Multivariate analysis identified delta-LMR as an independent prognostic factor for both FFM and OS. CONCLUSION: Delta-LMR is a simple and inexpensive biomarker that may be clinically useful for predicting FFM and OS in patients with HNC treated with RT.

Treatment of Primary Central Nervous System Germinomas With Short-course Induction Chemotherapy Followed by Low-dose Radiotherapy Without a Tumor Bed Boost: Prognostic Impact of Human Chorionic Gonadotropin.

OBJECTIVE: To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. METHODS: We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. RESULTS: Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (ß-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal ß-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased ß-hCG levels, those with ß-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). CONCLUSIONS: Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with ß-hCG levels <5 mIU/mL.

Proton versus photon radiotherapy for primary hepatocellular carcinoma: a propensity-matched analysis.

BACKGROUND: Proton radiotherapy has a dosimetric advantage over photon radiotherapy. Many retrospective studies have shown promising results with proton radiotherapy in treating hepatocellular carcinoma (HCC). However, clinical evidence demonstrating the benefit of protons over photons is still limited. We therefore compared the clinical outcomes of the two modalities using medical research databases from our medical foundation. METHODS: We conducted a propensity score-matched cohort study based on our multi-institution medical organization research database. From January 2007 to January 2018, a total of 413 patients (photon: 349; proton: 64) who were diagnosed with HCC and primarily treated with radiotherapy with curative intent were enrolled. Overall survival (OS) and radiation-induced liver disease (RILD) were assessed. Stratified analysis was also performed to evaluate the heterogeneous effects of the two arms. RESULTS: A total of 110 patients (photon: 55; proton: 55) were analyzed in the propensity-matched series. The matched groups were balanced for baseline tumor risk factors. Cox regression analysis revealed a significant survival benefit in the proton group (p = 0.032, HR 0.56, 95% CI 0.33-0.96). The median overall survival in the proton group was not reached and that in the photon group was 17.4 months. The biological equivalent dose of radiotherapy was significantly higher in the proton group than in the photon group (median, 96.56 Gray [relative biological effectiveness] vs. 62.5 Gray, p < 0.001). The risk of RILD was significantly lower in the proton group (11.8% vs. 36%, p = 0.004). CONCLUSIONS: Proton radiotherapy could deliver a higher radiation dose than photon radiotherapy without increasing the risk of RILD and result in a better overall survival rate for those diagnosed with HCC and treated with radiotherapy with curative intent.

Clinical Outcomes of Patients With Unresectable Cholangiocarcinoma Treated With Proton Beam Therapy.

OBJECTIVE: To investigate the clinical outcomes and failure patterns of patients with unresectable cholangiocarcinoma (CC) who had been treated with proton beam therapy (PBT). METHODS: The authors retrospectively examined 30 patients with unresectable CC who had undergone PBT between November 2015 and December 2017. Survival curves were plotted with the Kaplan-Meier method. Independent predictors of survival were identified by multivariate Cox proportional hazard regression analyses. Complications were assessed using the Common Terminology Criteria for Adverse Events v4.0. RESULTS: The median tumor size was 7 cm. Seventeen patients (56.7%) had regional lymph node metastases. The median radiation dose was 72.6 cobalt gray equivalents, and 23 patients (76.7%) received concurrent chemotherapy. The 1-year local control, regional control, and distant metastases-free rates were 88%, 86%, and 68%, respectively. The median overall survival and progression-free survival were 19.3 and 10.4 months, respectively. The median jaundice-free survival was 13 months, with a 1-year biliary tract infection (BTI)-free rate of 58%. Patients who received concurrent chemotherapy had a better median progression-free survival (12.1 vs. 4.7 mo). The most common form of acute toxicity from PBT was acute skin reactions which were rarely severe (grade III: 7% of patients). Three and 2 patients had grade III-IV toxicities and radiation-induced liver disease. There were no deaths caused by PBT or concurrent chemotherapy. CONCLUSIONS: PBT is clinically useful in patients with unresectable CC, even in the presence of large tumors or regional nodal metastases. Its use may induce durable symptom relief, without increasing acute or late toxicity.

Incidence of Cellulitis Following Acupuncture Treatments in Taiwan.

Background: Cellulitis is a complication of acupuncture, but the risk factors and annualized incidence remain unclear. Objective: This study analyzed the incidence and risk factors of cellulitis related to acupuncture in a cohort of one million participants derived from Taiwan's Longitudinal Health Insurance Database. Methods: We tracked this cohort between 1997 and 2012 and recorded all outpatient medical information including diagnosis and treatment. Patients were categorized according to age, gender, comorbidities, residential area, and number of acupuncture treatments. We compared the incidence and risk of cellulitis between different demographics and comorbidities by logistic regression analysis and adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). Results: We included 407,802 patients and 6,207,378 acupuncture treatments. The incidence of cellulitis after acupuncture was 64.4 per 100,000 courses of acupuncture treatment. The most common sites of cellulitis after acupuncture were the legs, feet, and face. Comorbidity was associated with post-acupuncture cellulitis; a multivariate logistic regression analysis showed that chronic kidney disease (aOR, 1.71; 95% CI, 1.55-1.88), rheumatoid arthritis (aOR, 1.86; 95% CI, 1.21-3.60), liver cirrhosis (aOR, 1.23; 95% CI, 1.15-1.32), diabetes mellitus (aOR, 1.69; 95% CI, 1.57-1.82), stroke (aOR, 1.44; 95% CI, 1.31-1.58), varicose veins (aOR, 2.38; 95% CI, 2.17-2.84), or heart failure (aOR, 1.81; 95% CI, 1.65-1.98) significantly increased cellulitis. Repeated exposure to acupuncture treatment was associated with an increased risk of cellulitis. Conclusions: A variety of chronic diseases may increase the risk of cellulitis after acupuncture. Physicians asked about past medical history before acupuncture might help to reduce cellulitis.

Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy.

PURPOSE: To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT). METHODS: This multicenter study included 136 patients with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined. RESULTS: The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A "volume-response" relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively. CONCLUSIONS: The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.

How small is TOO small? New liver constraint is needed- Proton therapy of hepatocellular carcinoma patients with small normal liver.

PURPOSE: This study evaluated the outcomes of hepatocellular carcinoma (HCC) patients with small normal liver volume (NLV) treated with proton beam therapy (PBT) and introduced estimated standard liver volume (eSLV) as a new constraint. MATERIALS AND METHODS: HCC patients with NLV < 800 cm3 and no distant metastasis who received treatment in our proton center were included. The doses of PBT were mainly 72.6 Gray equivalents (GyE) in 22 fractions and 66 GyE in 10 fractions according to tumor locations. The Urata equation was used to calculate eSLV. RESULTS: Twenty-two patients were treated between November 2015 and December 2016. The 1-year progression-free and overall survival rates were 40.4% and 81.8%, respectively. The 1-year in-field failure-free rate was 95.5%. NLV ranged from 483.9 to 795.8 cm3 (median = 673.8 cm3), eSLV ranged from 889.3 to 1290.0 cm3 (median = 1104.5 cm3), and the resulting NLV/eSLV ratio ranged from 44.3 to 81.2% (median = 57.7%). Non-irradiated liver volume (NILV) ranged from 232.9 to 531.6 cm3 (median = 391.2 cm3). The NILV/eSLV ratio ranged from 21.2 to 48.0% (median = 33.3%). NLV in the patients who received <30 GyE (rV30) ranged from 319.1 to 633.3 cm3 (median = 488.2 cm3), and their rV30/eSLV ratio ranged from 30.7 to 58.0%. None of our patients developed liver failure. One patient with initial abnormal liver enzyme levels developed non-classic radiation-induced liver disease (RILD). CONCLUSION: From the viewpoint of minimal liver toxicity occurring in our patients with NLV < 800 cm3, conventional liver constraints involving the use of absolute volume could not accurately predict the risk of RILD. It is reasonable to start using individualized constraints with eSLV for HCC patients undergoing PBT. According to the study results, an NILV/eSLV ratio of >20% and an rV30/eSLV ratio of >30% are acceptable.

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study.

BACKGROUND: Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. METHODS AND RESULTS: Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023). CONCLUSIONS: There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

Risk factors influencing complications of cardiac implantable electronic device implantation: infection, pneumothorax and heart perforation: a nationwide population-based cohort study.

As the number of cardiac implantable electronic devices (CIEDs) is increasing annually, CIED-related complications are becoming increasingly important. The aim of the study was to assess the risks associated with CIEDs by a nationwide database. Patients were selected from the Taiwan National Health Insurance Database. Admissions for CIED implantation, replacement, and revision were evaluated and the evaluation period was 14 years. Endpoints included CIED-related infection, pneumothorax, and heart perforation. The study included 40,608 patients with a mean age of 71.8 ± 13.3 years. Regarding infection, the incidence rate was 2.45 per 1000 CIED-years. Male gender, younger age, device replacement, and previous infection were risks for infection while old age and high-volume centers (>200 per year) were protectors. The incidence of pneumothorax was 0.6%, with an increased risk in individuals who had chronic obstructive lung disease (COPD) and cardiac resynchronized therapy (CRT). The incidence of heart perforation was 0.09%, with an increased risk in individuals who had pre-operation temporal pacing and steroid use. High-volume center was found to decrease infection rate while male gender, young people, and individuals who underwent replacements were associated with an increased risk of infection. Additionally, pre-operation temporal pacing and steroid use should be avoided if possible. Furthermore, COPD patients or those who accept CRTs should be monitored closely.