5-year Cumulative Incidence Rate Research Articles

Hepatitis B core-related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen-negative chronic hepatitis B patients.

The serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)-negative patients. Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients. Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (>6.8 vs 3.7log U/mL, P<0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis=3.5/4.7log U/mL, P=0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P<0.01) and even in non-cirrhosis patients. Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.

Stereotactic ablative radiotherapy in operable stage I NSCLC patients: Long-term results of the expanded STARS clinical trial.

8506 Background: We published a pooled analysis of 2 randomized trials (STARS/ROSEL) that compared lobectomy with mediastinal lymph node dissection (L-MLND) vs stereotactic ablative radiotherapy (SABR) in operable stage I NSCLC. There were no significant differences in disease progression but significantly higher 3-year overall survival (OS) in the SABR arm (95% vs 79%). Owing to concerns regarding the small sample size (n = 58), short follow-up (3 years), and non-uniform use of video-assisted thoracoscopic surgery (VATS), we expanded the STARS protocol to a single-arm SABR trial with a protocol-specified comparison to a published, longitudinally-followed institutional cohort of stage IA NSCLC status post VATS L-MLND (n = 229). Methods: Inclusion criteria were stage IA NSCLC (≤3 cm, N0M0 and staged by PET/CT with EBUS) with Zubrod performance status (PS) 0-2, baseline FEV1 &gt; 40% and DLCO &gt; 40% and deemed operable by a multidisciplinary team. SABR utilized 4-dimensional CT simulation and volumetric image guidance; 54 Gy in 3 fractions were delivered to planning target volumes (PTVs) located peripherally, or 50 Gy in 4 fractions to more central PTVs. All patients were followed by chest CT every three months for the first two years, every 6 months for another three years, and then annually. Non-inferiority of SABR could be claimed if the 3-year OS was not lower than the historical VATS L-MLND cohort by more than 12%. We conducted a risk-factor matched comparison study of the primary outcome between the SABR and the historical VATS L-MLND. Results: The median follow-up among the 80 SABR patients was 61 months (range, 34-79 months). The OS and progression-free survival (PFS) were 91% (95% CI: 85̃98%) and 80% (95% CI: 72̃89%) at 3 years, and 87% (95% CI: 79̃95%) and 77% (95% CI: 68̃87%) at 5 years, respectively. The 5-year cumulative incidence rate counting death as competing risk was 6.3% (95% CI: 2.3̃13.2%) local, 12.5% (95% CI: 6.4̃20.8%) regional, and 8.8% (95% CI: 3.8̃16.2%) distant (any recurrence 17.6% (95% CI: 10.1̃26.7%)). The 5 year cumulative incidence rate of second lung primary was 6.9% (95% CI: 2.5̃14.6%). There were 1.3% grade 3 and no grade 4-5 toxicities. The propensity score matched (age, gender, tumor size, histology, PS) comparison of SABR vs VATS L-MLND revealed no significant differences in PFS (p = 0.063), lung cancer-specific survival (p = 0.075), or cumulative incidence rates of local (p = 0.54), regional (p = 0.97), or distant failures (p = 0.33). The SABR arm was associated with significantly higher OS (91% vs 82% at 3 years and 87% vs 72% at 5 years; p = 0.012 from log-rank test). The hazard ratio was 0.411 (95% CI: 0.193̃0.875; p = 0.021). Conclusions: The long-term OS and PFS of SABR is not inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains a promising approach for this population, but multidisciplinary management is strongly recommended. Clinical trial information: NCT02357992.

Growth of vestibular schwannoma: long-term follow-up study using survival analysis.

A vestibular schwannoma (VS) is a benign nerve sheath tumor derived from the vestibular nerves. The growth rate of VS during long-term follow-up has not yet been fully evaluated. We aimed to investigate the growth rate of newly diagnosed VS and the related predictive factors for tumor growth. A retrospective review was performed using VS patients who underwent at least two magnetic resonance imaging (MRI) scans before tumor growth was observed. Tumor growth was defined as a size increase of more than 2mm in the longest diameter of the tumor. To assess the growth rate of VS and related factors, we assessed tumor growth using survival analysis. Survival analysis to assess the growth rate and Cox regression analysis were performed to find related factors. The study included 118 patients. The mean age of patients was 57.0 ± 12.9years. During the observation period, the 5-year cumulative growth incidence rate was 41.3% by survival analysis. Extrameatal tumor location and hearing loss were found to be associated with an increased hazard ratio (HR) for tumor growth. After long-term observation of VS, 41.3% of VS patients presented cumulative growth incidence rate in the first 5years after diagnosis. Extrameatal tumor location and hearing changes were related to subsequent tumor growth.

LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study

BackgroundLow-density lipoprotein to high density lipoprotein (LDL/HDL) cholesterol ratio has been reported to predict the risk of many metabolic diseases. However, the association between the LDL/HDL cholesterol ratio and nonalcoholic fatty liver disease (NAFLD) has not been established.MethodsA longitudinal cohort design was adopted in this study; 9767 non-obese subjects without NAFLD were included and analyzed. The subjects were grouped according to the quintile of LDL/HDL cholesterol ratio. The cumulative incidence of NAFLD and the independent effect of the LDL/HDL cholesterol ratio on NAFLD during 5 years of follow-up were calculated using the Kaplan-Meier method and Cox proportional-hazards regression model.ResultsDuring the 5-year follow-up period, 841 subjects were diagnosed with new-onset NAFLD, and the 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of NAFLD were 1.16, 4.65, 8.33, 12.43, and 25.14%, respectively. In the multivariable-adjusted Cox proportional-hazards regression model, the LDL/HDL cholesterol ratio was significantly associated with the risk for NAFLD (HR: 1.66, 95% CI: 1.38–1.99, P trend< 0.001), especially among young people (HR: 3.96, 95% CI: 1.50–10.46, P interaction< 0.05). Additionally, receiver operating characteristic curve analysis showed that the LDL/HDL cholesterol ratio was better than HDL cholesterol and LDL cholesterol in predicting new-onset NAFLD.ConclusionsLDL/HDL cholesterol ratio is an independent predictor of NAFLD in Chinese non-obese people with normal lipids, and its predictive value is higher than that of other lipoproteins. In clinical practice, the LDL/HDL cholesterol ratio can be used to identify people at high risk of NAFLD.

Clinical features and risk factors of gastric cancer detected by esophagogastroduodenoscopy in esophageal cancer patients.

Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients.

Impact of Body Mass Index on Local Recurrence according to Intrinsic Subtype Approximation in Korean Women with Early Stage Invasive Breast Cancer Receiving Contemporary Treatments.

Purpose: We investigated the prognostic impact of body mass index (BMI) on local recurrence (LR) according to intrinsic subtype in Korean women with early stage, invasive breast cancer.Materials and methods: We included 907 patients with pathological stage T1-2 and N0-1 breast cancer who underwent curative surgery between 2007 and 2012. Systemic treatments were administered in 876 patients (96.6%). In total, 701 patients (77.3%) received radiotherapy. Intrinsic subtypes were determined using immunohistochemical staining results.Results: During the median follow-up period of 72 months, LR as the first failure occurred in 29 patients, including 24 patients with isolated LR. The 5-year cumulative incidence rate of LR was 3.2% among all patients. In the luminal A subtype, a BMI of <18.5 kg/m2 was an independent risk factor for LR, as determined by a competing-risk regression model (relative risk, 3.33; p = 0.041). Severely obese patients (BMI >30 kg/m2) with the triple negative subtype had an increased risk of LR (relative risk, 3.81; p = 0.048).Conclusion: The present study identified traditionally underestimated risk groups for LR. BMI may diversely influence the rate of LR across intrinsic subtypes in Korean patients with breast cancer.

Nomograms for Estimating Cause-Specific Death Rates of Patients With Inflammatory Breast Cancer: A Competing-Risks Analysis.

Purpose:Inflammatory breast cancer (IBC) is a rare, aggressive and special subtype of primary breast cancer. We aimed to establish competing-risks nomograms to predict the IBC-specific death (BCSD) and other-cause-specific death (OCSD) of IBC patients.Methods:We extracted data on primary IBC patients from the SEER (Surveillance, Epidemiology, and End Results) database by applying specific inclusion and exclusion criteria. Cumulative incidence function (CIF) was used to calculate the cumulative incidence rates and Gray’s test was used to evaluate the difference between groups. Fine-Gray proportional subdistribution hazard method was applied to identify the independent predictors. We then established nomograms to predict the 1-, 3-, and 5-year cumulative incidence rates of BCSD and OCSD based on the results. The calibration curves and concordance index (C-index) were adopted to validate the nomograms.Results:We enrolled 1699 eligible IBC patients eventually. In general, the 1-, 3-, and 5-years cumulative incidence rates of BCSD were 15.3%, 41.0%, and 50.7%, respectively, while those of OCSD were 3.0%, 5.1%, and 7.4%. The following 9 variables were independent predictive factors for BCSD: race, lymph node ratio (LNR), AJCC M stage, histological grade, ER (estrogen receptor) status, PR (progesterone receptor) status, HER-2 (human epidermal growth factor-like receptor 2) status, surgery status, and radiotherapy status. Meanwhile, age, ER, PR and chemotherapy status could predict OCSD independently. These factors were integrated for the construction of the competing-risks nomograms. The results of calibration curves and C-indexes indicated the nomograms had good performance.Conclusions:Based on the SEER database, we established the first competing-risks nomograms to predict BCSD and OCSD of IBC patients. The good performance indicated that they could be incorporated in clinical practice to provide references for clinicians to make individualized treatment strategies.

Treatment-Related Deaths and Second Cancer Risk After Autologous Stem-Cell Transplantation for Hodgkin's Disease

Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure, its lethal toxicity and effects on the incidence of secondary cancers were studied. Data related to 467 French patients grafted from 1982 to 1995 for primary sensitive disease (PSD, 22%), primary refractory disease (PRD, 18%), first relapse (R1, 45%), or subsequent relapses (R2, 15%) were analyzed. Grafted patients (PSD, PRD, and R1; n = 393) were matched (3 controls for 1 case) on age, gender, clinical stage, B symptoms, and time at risk with 1179 conventionally treated patients issued from international databases. The proportional hazards (Cox) model was used to assess relative risks (RR). Among grafted patients, 8% died of toxicity related to the procedure, and 18 secondary cancers occurred leading to a 5-year cumulative incidence rate of 8.9%. In this series, risk factors for second cancer were age ≥40 years (RR = 3.73, P= .007) and the use of peripheral blood stem cells as source of graft (RR = 3.10, P = .03). Among grafted and matched ungrafted patients, risk factors for the development of secondary cancer were age ≥40 years (RR = 2.90, P < .001), relapse versus no relapse (RR = 5.22, P = .006), PRD versus other patients (RR = 3.86, P = .033), and grafted versus ungrafted patients (RR = 2.04, P = .024). Solid tumors were more frequent in grafted than in ungrafted patients (RR = 5.19, P= .001) although the incidence of myelodysplasia and acute myeloid leukemia was similar in the two groups. We conclude that high-dose chemotherapy administered as first-line treatment or after relapse is associated with an acceptable toxic death rate. The risk of secondary myelodysplasia or acute myeloid leukemia is not significantly increased after autologous stem-cell transplantation for HD, whereas an increased risk of solid tumors exists. The peripheral blood stem-cell–associated risk of secondary cancer among grafted patients needs further investigations.© 1998 by The American Society of Hematology.

Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study

Simple SummarySarcopenia is prevalent in patients with liver cirrhosis. It has been well-known that cirrhotic patients with sarcopenia had poorer survival as compared to those without it, and expression of serum myostatin is associated with sarcopenia. In this study, we aimed to evaluate whether serum myostatin is associated with hepatocellular carcinoma development in patients with alcoholic cirrhosis or not. We found that serum myostatin is associated with hepatocellular carcinoma development in a large cohort of patients with alcoholic cirrhosis. Among patients with similar residual liver function or similar risk of developing hepatocellular carcinoma using other models, higher serum myostatin was significantly associated with a higher risk of developing hepatocellular carcinoma. In addition, patients with more advanced hepatic fibrosis had significantly higher serum myostatin than those with less advanced hepatic fibrosis. Thus, serum myostatin as a prognostic marker can be useful to identify high-risk patients who need stringent surveillance for hepatocellular carcinoma.Background and Aim: Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC). Methods: This retrospective, multicenter study assessed 1077 Asian ALC patients enrolled from 2007 to 2017. The primary endpoint was the development of HCC within 5 years. Cox proportional hazards model analyses were used to assess the association of serum myostatin levels and HCC development. The time-dependent areas under the receiver operating characteristic curve (AUROC) of serum myostatin for 5-year HCC development were calculated. Serum myostatin levels were measured using an enzyme-linked immunosorbent assay with samples collected on the index date. Results: During a median follow-up of 2.5 years, 5-year cumulative HCC incidence rates were 6.7% in the total population. The median level of serum myostatin was 3.3 ng/mL (interquartile, 2.1–5.2 ng/mL). The AUROC of serum myostatin for 5-year HCC development was 0.78 (95% confidence interval [CI], 0.76–0.81). In Cox proportional hazards model analyses, age, gender, platelet counts, and serum myostatin levels were independent risk factors for HCC development (adjusted hazard ratios [HRs] of age, male gender, platelet counts, and serum myostatin: 1.03, 2.79, 0.996, 1.18, respectively; all p < 0.05). Patients with high myostatin levels had a significantly higher risk of 5-year HCC development than those with low myostatin levels (HR 7.53, p < 0.001). Conclusion: Higher serum myostatin levels were significantly associated with a higher risk of developing HCC in ALC patients, which could identify high-risk patients who need stringent surveillance.

Inhaled corticosteroids and the risk of type 2 diabetes among Swedish COPD patients

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.

Long-term outcomes of moderately hypofractionated radiotherapy (67.5\xa0Gy in 25 fractions) for prostate cancer confined to the pelvis: a single center retrospective analysis

BackgroundThere is an increasing application of moderately hypofractionated radiotherapy for prostate cancer. We presented our outcomes and treatment-related toxicities with moderately hypofractionated (67.5 Gy in 25 fractions) radiotherapy for a group of advanced prostate cancer patients from China.MethodsFrom November 2006 to December 2018, 246 consecutive patients with prostate cancer confined to the pelvis were treated with moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions). 97.6% of the patients received a different duration of androgen deprivation therapy. Failure-free survival (FFS), prostate cancer-specific survival (PCSS), overall survival (OS), and cumulative grade ≥ 2 late toxicity were evaluated using the Kaplan–Meier actuarial method. Prognostic factors for FFS, PCSS, and OS were analyzed.ResultsThe median follow-up time was 74 months (range: 6–150 months). For all patients, the 5- and 10-year FFS rates were 80.0% (95% CI: 74.7–85.7%) and 63.5% (95% CI 55.4–72.8%). The failure rates for the intermediate, high-risk, locally advanced, and N1 groups were 6.1%, 13.0%, 18.4%, and 35.7%, respectively (P = 0.003). Overall, 5- and 10-year PCSS rates were 95.7% (95% CI 93.0–98.5%) and 88.2% (95% CI 82.8–93.8%). Prostate cancer-specific mortality rates for the high-risk, locally advanced, and N1 groups were 4.0%, 8.2%, and 23.8%, respectively (P < 0.001). Overall, 5- and 10-year actuarial OS rates were 92.4% (95% CI 88.8–96.1%) and 72.7% (95% CI 64.8–81.5%). High level prostate-specific antigen and positive N stage were significantly associated with worse FFS (P < 0.05). Advanced T stage and positive N stage emerged as worse predictors of PCSS (P < 0.05). Advanced age, T stage, and positive N stage were the only factors that were significantly associated with worse OS (P < 0.05). The 5-year cumulative incidence rate of grade ≥ 2 late GU and GI toxicity was 17.8% (95% CI 12.5–22.7%) and 23.4% (95% CI 17.7–28.7%), respectively.ConclusionsModerately hypofractionated radiotherapy (67.5 Gy in 25 fractions) for this predominantly high-risk, locally advanced, or N1 in Chinese patients demonstrates encouraging long-term outcomes and acceptable toxicity. This fractionation schedule deserves further evaluation in similar populations.

Prognostic Factors in Patients with Rhabdomyosarcoma Using Competing-Risks Analysis: A Study of Cases in the SEER Database.

Background Rhabdomyosarcoma (RMS) is a rare malignant soft-tissue sarcoma characterized by a poor outcome and unclear prognostic factors. This study applied a competing-risks analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database to RMS patients, with the aim of identifying more accurate prognostic factors. Methods Data of all patients with RMS during 1986–2015 were extracted from the SEER database. We used the competing-risks approach to calculate the cumulative incidence function (CIF) for death due to rhabdomyosarcoma (DTR) and death from other causes (DOC) at each time point. The Fine–Gray subdistribution proportional-hazards model was then applied in univariate and multivariate analyses to determine how the CIF differs between groups and to identify independent prognostic factors. The potential prognostic factors were analyzed using the competing-risks analysis methods in SAS and R statistical software. Results This study included 3399 patients with RMS. The 5-year cumulative incidence rates of DTR and DOC after an RMS diagnosis were 39.9% and 8.7%, respectively. The multivariate analysis indicated that age, year of diagnosis, race, primary site, historic stage, tumor size, histology subtype, and surgery status significantly affected the probability of DTR and were independent prognostic factors in patients with RMS. A nomogram model was constructed based on multivariate models for DTR and DOC. The performances of the two models were validated by calibration and discrimination, with C-index values of 0.758 and 0.670, respectively. Conclusions A prognostic nomogram model based on the competing-risks model has been established for predicting the probability of death in patients with RMS. This validated prognostic model may be useful when choosing treatment strategies and for predicting survival.

CML-105: A Validation of Vascular Adverse Events Risk Assessment Method for Japanese CML Patients with Tyrosine Kinase Inhibitors

Background and Aim Tyrosine kinase inhibitors (TKIs) have substantially improved the prognosis of chronic myeloid leukemia (CML). However, TKIs can cause serious vascular adverse events (VAEs) such as ischemic heart disease (IHD), peripheral artery occlusive disease (PAOD), cerebral infarction (CI), and pulmonary embolism (PE). The Framingham general cardiovascular risk scores (FRS), Suita score (SS), and SCORE (Systematic Coronary Risk Evaluation) system are commonly used to predict the incidence of cardiovascular events, but their usefulness as evaluation methods for patients with CML is unknown. We aimed to determine the appropriateness of these evaluation methods for a Japanese CML cohort. Methods We retrospectively surveyed patients with CML who visited our institute between January 2003 and March 2020. All patients were evaluated using the three risk assessment tools (FRS, SS, low-risk SCORE chart). To predict the 5-year event-free survival, we determined the cut-off values of each scoring system from the receiver operating characteristic analysis (ROC) curve. Results Sixty-nine patients with CML (38 males) were registered. Their median age was 66 years (range, 25–91years), and the median follow-up time was 48 months. Eight patients (2 males) had VAEs (3 IHD, 2 PAOD, 1 CI, 1 PE, and 1 sudden death). Four patients were treated with nilotinib, 2 with imatinib,1 with dasatinib, and 1 with bosutinib. The cut-off values obtained from the ROC curve for the SS and SCORE chart were 45 and 2, respectively. The sensitivity, specificity, and area under the curve (AUC) were 0.574, 0.875, and 0.713 for the SS and 0.689, 0.750, and 0.755 for the SCORE chart, respectively. We were unable to calculate the FRS because of the small number of men with thrombosis. However, the cut-off value was 11 points when limited to the female patients. The 5-year cumulative incidence rates of VTEs were 14.9% and 0% in patients with SS of ≥45 and Conclusion For this Japanese CML cohort, we propose that the SS and SCORE chart are valid evaluation methods for VAE assessment.

Quantifying the Impact of Axillary Surgery and Nodal Irradiation on Breast Cancer-Related Lymphedema and Local Tumor Control: Long-Term Results From a Prospective Screening Trial.

To independently evaluate the impact of axillary surgery type and regional lymph node radiation (RLNR) on breast cancer-related lymphedema (BCRL) rates in patients with breast cancer. From 2005 to 2018, 1,815 patients with invasive breast cancer were enrolled in a lymphedema screening trial. Patients were divided into the following 4 groups according to axillary surgery approach: sentinel lymph node biopsy (SLNB) alone, SLNB+RLNR, axillary lymph node dissection (ALND) alone, and ALND+RLNR. A perometer was used to objectively assess limb volume. All patients received baseline preoperative and follow-up measurements after treatment. Lymphedema was defined as a ≥ 10% relative increase in arm volume arising > 3 months postoperatively. The primary end point was the BCRL rate across the groups. Secondary end points were 5-year locoregional control and disease-free-survival. The cohort included 1,340 patients with SLNB alone, 121 with SLNB+RLNR, 91 with ALND alone, and 263 with ALND+RLNR. The overall median follow-up time after diagnosis was 52.7 months for the entire cohort. The 5-year cumulative incidence rates of BCRL were 30.1%, 24.9%, 10.7%, and 8.0% for ALND+RLNR, ALND alone, SLNB+RLNR, and SLNB alone, respectively. Multivariable Cox models adjusted for age, body mass index, surgery, and reconstruction type showed that the ALND-alone group had a significantly higher BCRL risk (hazard ratio [HR], 2.66; P = .02) compared with the SLNB+RLNR group. There was no significant difference in BCRL risk between the ALND+RLNR and ALND-alone groups (HR, 1.20; P = .49) and between the SLNB-alone and SLNB+RLNR groups (HR, 1.33; P = .44). The 5-year locoregional control rates were similar for the ALND+RLNR, ALND-alone, SLNB+RLNR, and SLNB-alone groups (2.8%, 3.8%, 0%, and 2.3%, respectively). Although RLNR adds to the risk of lymphedema, the main risk factor is the type of axillary surgery used.

Optimal breast reconstruction type for patients treated with neoadjuvant chemotherapy, mastectomy followed by radiation therapy.

To explore the optimal type of breast reconstruction and the time interval to postmastectomy radiotherapy (PMRT) associated with lower complications in breast cancer patients receiving neoadjuvant chemotherapy. We reviewed the medical records of 300 patients who received neoadjuvant chemotherapy, mastectomy with breast reconstruction and PMRT at our institution from 2000 to 2017. Reconstruction types included autologousflaps (AR), single-stage-direct-to-implant and two-stages expander/implant (TE/I). The primary endpoint was therate of reconstruction complications including infection, skin and fat necrosis. Subgroup analysis compared rates of capsular contracture, implant rupture, implant exposure and overall implant failure in single-stage-direct-to-implant to TE/I. The secondary endpoint was identifyingthe time interval between surgerywith immediate implant-based reconstruction and PMRT associated with lower probability of implant failure. Logistic regression models, Kaplan-Meier estimates and Polynomial regression were used to assess endpoints. The median follow-up was 43.5months. 29.3%, 28.3% and 42.4% of the cohort had AR, TE/I and single-stage-direct-to-implant D, respectively. The 5-year cumulative incidence rate of complications was 14.0%, 29.7% and 19.4% for AR, TE/I and single-stage-direct-to-implant, respectively (Log rank p = 0.02). Multivariate analysis showed significant association between TE/I and higher risk of infection (OR 8.1, p = 0.009) compared to AR, while single-stage-direct-to-implant and AR were comparable (OR 3.2, p = 0.2). On subgroup analysis, TE/I was significantly associated with higher rates of implant failure. The mean wait time to deliver PMRT after immediate reconstruction with no adjuvant chemotherapy was 8.4 and 10.7weeks in single-stage-direct-to-implant and TE/I, respectively (p < 0.005). Delivering PMRT after 8weeks of surgery yielded 10% probability of reconstruction failure in single-stage-direct-to-implant versus 40% in TE/I. In comparison to two stages reconstruction, single-stage-direct-to-implant following neoadjuvant chemotherapy has lower complications and offers timely delivery of PMRT.

Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study.

Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study. Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC. 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %. Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.

Incidence of rhegmatogenous retinal detachment after bag-in-the-lens IOL implantation: extended follow-up in a larger cohort of patients.

To report the incidence of rhegmatogenous retinal detachment (RRD) and associated risk factors after cataract surgery using the bag-in-the-lens (BIL) intraocular lens (IOL) implantation technique. Department of Ophthalmology, Antwerp University Hospital, Belgium. Prospective cohort study. All consecutive BIL IOL surgeries performed between January 2001 and December 2010 were included, with the exclusion of combined procedures and IOL exchanges. The incidence of RRD was reported first in the total cohort, then in a subgroup of patients with 1 year to 5 years of follow-up, and finally in the group remaining after exclusion of all risk factors, except gender. Risk factors associated with RRD were examined using multiple Cox regression analysis with a random intercept. Rhegmatogenous RD was diagnosed in 36 eyes (1.06%) of 3385 BIL cases, with a mean follow-up of 48.28 ± 40.05 months (range 0 to 195 months). The 2-year cumulative RRD incidence rate was 0.66% (17 cases in 1024 eyes; 0.00% in patients without risk factors). The 5-year cumulative RRD incidence rate was 1.17% (26 cases in 931 eyes; 0.15% without risk factors). Five risk factors were confirmed: male sex, age less than 60 years at the time of surgery, axial length 25.0 mm or greater, a history of contralateral RD, and intraoperative surgical complications. The incidence of RRD after BIL IOL implantation is comparable with that of lens-in-the-bag (LIB) implantation. This larger study provided a longer follow-up and suggested that RRD incidence is even lower than that previously reported. This study also confirmed intraoperative surgical complications as an additional risk factor for RRD development, as already described with LIB implantation.

Biological subtype predicts locoregional recurrence after postmastectomy radiotherapy in Chinese breast cancer patients.

AimTo investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT).Methods and MaterialsAbout 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A‐like, Luminal B‐like, HER2‐positive, and triple‐negative breast cancer (TNBC). Local and regional recurrence (LRR) cumulative incidences were calculated by competing risks methodology and the power of prognostic factors was examined by Gray's test and the test of Fine and Gray.ResultsThe median follow‐up was 70.9 months. About 34 LRR events occurred. For Luminal A, Luminal B, HER2‐positive, and TNBC patients, the 5‐year LRR cumulative incidence rates were 1.57%, 4.09%, 10.74%, and 10.28%. Compared with Luminal A, HER2‐positive subtype and TNBC had a significant increased risk of LRR (HR was 5.034 and 5.188, respectively). In univariate analysis, predictive factors for higher LRR were HER2‐positive subtype (HR = 4.43, P < .05), TNBC (HR = 4.70, P < .05), and pN3 (HR = 5.83, P < .05). In the multivariate model, HER2‐positive subtype (HR = 5.034, P < .05), TNBC (HR = 5.188, P < .05), and pN3 (HR = 9.607, P < .01) were independent predictors of LRR. LRR without trastuzumab was similar to that of TNBC (without vs TNBC, 17.88% vs 10.28%, P > .05) in HER2‐positive subtype patients, while LRR with trastuzumab was approximate to Luminal A (with vs Luminal A, P > .05). Additionally, endocrine therapy also significantly reduced LRR incidence in the luminal subtype cohort (without vs with therapy, 6.25% vs 2.89%, HR = 0.365, P < .1).ConclusionsBiological subtype was a prognostic factor of LRR in the PMRT setting among Chinese breast cancer patients.

Successful Eradication of Helicobacter pylori Could Prevent Metachronous Gastric Cancer: A Propensity Matching Analysis

Background and Aim: Helicobacter pylori is the leading cause of gastric cancer, but it is still uncertain whether eradicating H. pylori in early gastric cancer (EGC) patients who underwent endoscopic resection can prevent metachronous gastric cancer (MGC). This study aimed to investigate the effect of H. pylori eradication to prevent MGC after endoscopic submucosal dissection (ESD). Methods: In this propensity-matched retrospective observational study, 770 patients with EGC who received ESD were enrolled. The outcome was the incidence of MGC; this was compared between the persistent and eradicated groups. Results: MGC was detected in 27 patients (7.8%) during a median period of 39.0 months (range 26.0–64.0). After propensity matching, 126 pairs of patients in each group were analyzed. The 5-year cumulative incidence rates of MGC were 13.2 and 3.9% in the persistent and eradicated groups, respectively (p= 0.021, log-rank test). On multivariate analysis, H. pylori eradication prevented MGC significantly (hazard ratio [HR] 0.32; p = 0.029). The results remained robust after inverse probability of treatment weighting analysis (HR 0.30; p = 0.020). Conclusions: Successful H. pylori eradication could prevent MGC after ESD for EGC.

Risk of developing metachronous advanced colorectal neoplasia after resection of low-risk diminutive versus small adenomas

Current postpolypectomy guidelines classify 1 to 2 diminutive (1-5mm) nonadvanced adenomas (NAAs) and 1 to 2 small (6-9mm) NAAs as low-risk adenomas and recommend the same surveillance interval for both lesions. We compared the risk of metachronous advanced colorectal neoplasia (ACRN) for both groups. We studied 8602 patients who underwent removal of≥1 NAA and follow-up colonoscopic surveillance. Patients were categorized into 4 groups based on size and number of baseline NAAs: group 1,≤2 diminutive NAAs (n= 6379); group 2,≤2 small NAAs (n= 1672); group 3,≥3 diminutive NAAs (n= 293); and group 4,≥3 small NAAs (n= 258). Size was classified based on the largest NAA. The 5-year cumulative incidence rates of metachronous ACRN in groups 1, 2, 3, and 4 were 2.7%, 5.1%, 10.7%, and 15.1%, respectively. Groups 2, 3, and 4 had a higher risk of metachronous ACRN than group 1. Compared with group 1, the adjusted hazard ratios for metachronous ACRN were 2.06 (95% confidence interval [CI], 1.46-2.91) for group 2, 2.75 (95% CI, 1.53-4.96) for group 3, and 4.49 (95% CI, 2.62-7.70) for group 4. However, the risk of metachronous ACRN was not significantly different between groups 3 and 4 (adjusted hazard ratio, 1.62; 95% CI, .76-3.44). Among patients with≤2 NAAs, patients with 1- to 5-mm NAAs had a lower risk of metachronous ACRN than those with 6- to 9-mm NAAs. The guidelines should consider extending surveillance intervals in patients with≤2 diminutive NAAs.