Lugol chromoendoscopy is widely used for screening esophageal squamous cell neoplasms (ESCNs) and evaluating dissection margins during endoscopic submucosal dissection (ESD). However, morphological variations may arise following treatment for synchronous cancers. This study aimed to assess the impact of chemotherapy on Lugol chromoendoscopy findings during both screening and ESD. From August 2009 to March 2024, ESCN patients undergoing esophageal ESD were enrolled. Lugol chromoendoscopy findings were analyzed based on four criteria: iodine staining, lesion size, margin assessment, and the pink-color sign. Findings from screening endoscopy and ESD were compared, and medical records were reviewed for chemotherapy and radiation data. A literature review was also conducted to explore the potential effects of chemotherapy on Lugol chromoendoscopy findings. Among the 162 patients in this ESD cohort, 32 (19.8%) demonstrated notable differences between initial and follow-up Lugol chromoendoscopy. Among them, 14 (43.8%) had undergone chemotherapy prior to ESD, while 26 received chemotherapy within 2 months before ESD. A significant proportion (53.8%) of chemotherapy-treated patients exhibited faded chromoendoscopy findings (p < 0.01), despite no esophageal radiation exposure. Literature review findings supported our observation that chemotherapy may reduce Lugol voiding lesions. These findings suggest that chemotherapy influences lesion size and morphology during Lugol chromoendoscopy, underscoring the importance of careful timing and interpretation in these patients.

Esophageal squamous cell carcinoma (ESCC) with adjacent structure invasion (T4b), affecting areas such as the aorta, vertebral body, or trachea, is associated with a poor prognosis, and the optimal treatment strategy remains unclear. While chemotherapy is considered standard, radiation therapy is often avoided due to the risk of severe complications, including tracheoesophageal fistula. This 10-year cohort study investigated clinical outcomes and prognostic factors in patients with T4b ESCC. From October 2011 to May 2022, 471 ESCC patients were diagnosed at our institution, of whom 130 (27%) had T4b disease. First-line treatments included definitive chemoradiotherapy (n = 82), chemotherapy alone (n = 15), radiotherapy alone (n = 5), immunotherapy clinical trials (n = 7), palliative surgery (n = 2) and best supportive care (n = 19). Patients treated with definitive chemoradiotherapy demonstrated significantly longer overall survival compared with those receiving monotherapy. The mean survival was 24.2 months in the chemoradiotherapy group, versus 4.2 months with chemotherapy alone and 8.5 months with radiotherapy alone (p < 0.001). Esophageal fistula developed in 22 patients (16.9%), with 5 cases identified at diagnosis and 17 occurring during follow-up. Chemotherapy alone was associated with a significantly higher risk of fistula formation compared with chemoradiotherapy (adjusted hazard ratio = 11.22, p = 0.01). The presence of a fistula was correlated with worse survival outcomes (median survival of 8.9 months versus 12.2 months, p = 0.03). These findings suggest that definitive chemoradiotherapy may enhance survival in T4b ESCC patients.

This study examined whether CT metrics at the 12th thoracic vertebra (T12) can replace those at the 3rd lumbar vertebra (L3) for diagnosing sarcopenia, and analyzed their impact on outcomes in esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed 405 CT scans (person-times) of 206 ESCC patients (stages II–IV) who had received chemoradiotherapy (CRT). Metrics including Skeletal Muscle Index (SMI), Skeletal Muscle Attenuation (SMA), Intramuscular Adipose Content (IMAC), and Visceral-to-Subcutaneous Adipose Tissue Ratio (VSR) were measured at both T12 and L3. These were compared with clinical outcomes. Significant correlations were found between body composition parameters measured at T12 and L3, with Spearman’s coefficients of 0.62 for SMI, 0.72 for SMA, 0.59 for IMAC, and 0.46 for VSR (all p < 0.01). After adjusting for age, gender, and tumor stage, a low post-CRT T12 SMI was significantly associated with reduced overall survival (adjusted hazard ratio = 1.56, p = 0.04), which corresponded to low post-CRT L3 SMI (adjusted hazard ratio = 1.65, p = 0.04). We concluded that measuring skeletal muscle at T12 can effectively diagnose sarcopenia using chest-only CT scans. Post-CRT T12 SMI may serve as a prognostic indicator for ESCC patients. Question Assessing sarcopenia in esophageal cancer patients is crucial for prognosis, yet traditional metrics rely on the 3rd lumbar vertebra, which may not be optimal. Findings Our study demonstrates that the muscle index at the 12th thoracic vertebra correlates well with that of the 3rd lumbar vertebra, effectively predicting patient survival. Clinical relevance Evaluating sarcopenia at the 12th thoracic vertebra via chest CT offers a reliable prognostic tool for esophageal squamous cell carcinoma patients, potentially improving survival predictions after chemoradiotherapy.

BackgroundMore than 50% of esophageal cancer patients are diagnosed with advanced diseases and commonly experience dysphagia, some of whom even have tracheoesophageal fistula. Self-expandable metal stent (SEMS) is one of the recommended palliative methods, although complications such as chest pain and stent migration are not uncommon. The goal of this study was to examine the predictors of stent migration.MethodsWe conducted a retrospective cohort study to include patients with esophageal cancer and dysphagia/tracheoesophageal fistula. Clinicopathological information, stent characteristics and patient outcomes were collected for analysis, while side-effects of SEMS were recorded, potential predictors were examined, and patients’ nutritional outcomes were compared in the migration and non-migration groups.ResultsA total of 54 patients with esophageal cancer who received fully covered SEMS between 2013 and 2022 were included. We found tumor across the esophagogastric junction (adjusted odds ratio (OR) = 32.64, P = 0.01) and the female sex (adjusted OR = 12.5, P = 0.02) were significant predictors for stent migration. There was a decreasing tendency in body mass index/body weight in migration and non-migration groups, but the former had a steeper downslope.ConclusionFully covered SEMS is a safe and effective strategy to palliate dysphagia or fistula. Tumor across esophagogastric junction and the female sex were higher risk predictors of stent migration. A careful patient selection would optimize the effects of SEMS placement, especially in those with short-expected lifespan.

BACKGROUND:Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. METHODS:A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS:Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. CONCLUSION:The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. CLINICALTRIALS.GOV IDENTIFIER:NCT03162510.

[This corrects the article DOI: 10.1371/journal.pone.0258040.].

Objective: The current study aimed to investigate the basic principles and clinical applications, including the selection of proper candidates, follow-up strategies, and radiation protection issues relating to peptide receptor radionuclide therapy (PRRT). Data Sources and Study Selection: We searched various scientific databases using specific keywords. Results: Due to the overexpression of somatostatin receptors in neuroendocrine tumors (NETs), PRRT is currently considered an important therapeutic modality for the management of NETs. Conclusion: PRRT incorporates the systemic administration of a tumor-targeting radiolabeled peptide to patients with tumors, allowing for more precise delivery of radiation doses to tumor sites while sparing normal tissues.

Abstract Introduction Accurate identification of apnea types is crucial for effective diagnosis and management of sleep-disordered breathing. The Belun Sleep System (BLS-100, a.k.a., Belun Ring) is an FDA-cleared home sleep apnea testing system (K222579) comprising an adjustable ring-shaped wearable, a cradle, and two deep learning-powered algorithms. The Belun Cor, a novel subxiphoid sensor equipped with accelerometry, can detect respiratory effort, respiratory rate, body position, and facilitates the detection of central events. This preliminary analysis aims to assess the performance of the integrated BLS-100 in detecting apnea events containing central components. Methods This interim analysis evaluated the performance of BLS-100 in a clinical cohort of hospitalized patients admitted for acute ischemic stroke. Eligible patients underwent in-lab polysomnography (PSG) alongside concurrent BLS-100 testing. PSG scoring adhered to the latest AASM scoring manual, with scoring technicians blinded to the BLS-100 results. The BLS-100 derived total sleep time (bTST), sleep stages (bSTAGE), apnea-hypopnea index (bAHI), and combined central and mixed apnea index (bCMAI). Results As of 12/17/2023, 25 consecutive Taiwanese patients were enrolled. Four patients were excluded due to short bTST< 120 mins. The analysis was conducted on 21 patients. M:F 19:2; age 59.7; PSG TST 270 ± 61.9 mins; PSG AHI 27.0 (1.4-81.9) with 3 normal, 3 mild, 7 moderate, and 8 severe OSA cases. The mean PSG central apnea index (PSG-CAI) was 4.8 (0.0-34.0), with 5 patients having PSG-CAI≥5. The mean PSG central and mixed apnea index (PSG-CMAI) was 8.4 (0.0-47.3). Pearson correlation coefficients between PSG-CAI and bCMAI, as well as PSG-CMAI and bCMAI, were 0.939 (P< 0.001) and 0.982 (P< 0.001), respectively. Using bCMAI≥5 to predict PSG-CAI≥5, the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen’s Kappa were 0.81, 1.00, 0.75, 0.56, 1.00, and 0.59, respectively. Similarly, using bCMAI≥5 to predict PSG-CMAI≥5, the corresponding values were 0.86, 0.88, 0.85, 0.78, 0.92, and 0.70, respectively. Conclusion Early findings indicate that the BLS-100 with Belun Cor shows promising performance in identifying apnea events that include central components. An elevated bCMAI serves as a valuable indicator for clinicians, signaling the presence of central or mixed apneas. Support (if any) Case Western Reserve University-Taipei Medical University Pilot Award

BACKGROUND AND AIM:Oral and esophageal cancers are globally prevalent, especially in East Asia. Over half of head and neck cancer patients developing second primary esophageal cancer (SPEC) were initially diagnosed with oral cavity cancer (OCC). This study assessed the cost-effectiveness of universal endoscopic screening for early SPEC prevention in newly diagnosed OCC patients at different stages. METHODS:This study employed Markov cohort models to evaluate the cost-effectiveness of endoscopic SPEC screening post-OCC diagnosis (stages 0 to IV) between screened and non-screened groups. Four surveillance frequencies were assessed: (i) one time, (ii) annual for 3 years, (iii) annual for 10 years, and (iv) annual for life. A hypothetical cohort of 100 000 cases across stages was compared for costs and quality-adjusted life-years (QALYs), discounted annually at 3%. RESULTS:All four screening strategies were beneficial for all OCC stages, especially for early-stage patients, resulting in higher QALYs. Lifetime/annual screening from the payer's perspective proved most favorable, with incremental QALYs of 1.23 at stage 0 and 0.06 at stage IV. Incremental costs for this strategy ranged from NTD 121 331 (USD 4044) at stage 0 to NTD 13 032 (USD 434) at stage IV. Both incremental costs and incremental cost-effectiveness ratio (ICER) values indicated cost savings from a societal perspective. The ICER values ranged from NTD -626 440 (USD -20 881) at stage 0 and NTD -475 021 (USD -15 834) at stage IV. CONCLUSIONS:Overall, our study provided cost-effectiveness evidences to understanding the cost-effectiveness of endoscopic screening in OCC patients, particularly emphasizing the benefits of early and consistent screening.

Background: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. Methods: In total, 111 medically operable, non -cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal -of -surgery group). Predictors and survival data were analyzed. Results: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal -ofsurgery groups, the 5 -year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression -free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal -of -surgery group. Conclusion: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal -of -surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy. Copyright 2023, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

BACKGROUND:This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed.METHODS:Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry.RESULTS:Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively.CONCLUSIONS:The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Curriculum learning has proven highly effective to speed up training convergence with improved performance in a variety of tasks. Researchers have been studying how a curriculum can be constituted to train reinforcement learning (RL) agents in various application domains. However, discovering curriculum sequencing requires the ranking of sub-tasks or samples in order of difficulty, which is not yet sufficiently studied for robot navigation problems. It is still an open question what navigation strategies can be learned and transferred during multi-stage transfer learning from easy to hard. Furthermore, despite of some attempts of learning real robot manipulation tasks using curriculum, most of existing works are limited to toy or simulated settings rather than realistic scenarios. To address those issues, we first investigated how the model convergence in diverse environments relates to the navigation strategies and difficulty metrics. We found that only some of the environments can be trained from scratch, such as in a relatively open tunnel-like environment that only required wall following. We then carried out a two-stage transfer learning for more difficult environments. We found such approach effective for goal navigation, but failed for more complex tasks where movable obstacles may be on the navigation path. To facilitate more complex policies in the navigation among movable obstacles (NAMO) task, another curriculum with distance and pace functions appropriate to the difficulty of the environment was developed. The proposed scheme was proved effective and the strategies learned were discussed via comprehensive evaluations conducted in simulated and real environments.

A 58-year-old man presented with dysphagia that had persisted for 6 months. EGD showed a protruding tumor in the cervical to upper esophagus (A) and another smaller tumor in the lower esophagus (18-22 cm and 38 cm from the incisors). Pathologic examination of a biopsy specimen showed squamous cell carcinoma. CT of the chest (B) and positron emission tomography—CT (PET-CT) revealed T3N1M0, stage III disease. He received definitive chemoradiotherapy with 2 cycles of platinum and 5-fluorouracil plus radiotherapy 5,000 cGy in 25 fractions and achieved partial response. A serial follow-up EGD showed nearly total tumor regression, but biopsy of the discolored mucosa at 25 and 34 cm from the incisors showed high-grade dysplasia. He refused surgery because total laryngectomy was required, and he received further chemotherapy for 18 months. EUS disclosed no obvious mass lesion, with intact muscularis propria layer; CT and PET-CT revealed persistent tumor shrinkage at the upper third of the esophagus without metastasis. The tumor was clinically downstaged to T1aN0M0. Endoscopic submucosal dissection (ESD) for residual esophageal neoplasm (C) was performed smoothly. The final pathologic report (D) showed high-grade intraepithelial neoplasia with negative margins. We assessed his condition at regular follow-up visits with EGD, CT, and PET after ESD. Neither local recurrence nor distant metastasis of the esophageal cancer has been observed for 22 months.

We present an unsupervised learning denoising method, RepE (representation and enhancement), designed for nonlinear optical microscopy images, such as second harmonic generation (SHG) and two-photon fluorescence (TPEF). Addressing the challenge of effectively denoising images with various noise types, RepE employs an encoder network to learn noise-free representations and a reconstruction network to generate denoised images. It offers several key advantages, including its ability to (i) operate without restrictive statistic assumptions, (ii) eliminate the need for clean-noisy pairs, and (iii) requires only a few training images. Comparative evaluations on real-world SHG and TPEF images from esophageal cancer tissue slides (ESCC) demonstrate that our method outperforms existing techniques in image quality metrics. The proposed method provides a practical, robust solution for denoising nonlinear optical microscopy images, and it has the potential to be extended to other nonlinear optical microscopy modalities.

Fig. S1. Representative mass spectrometry data of methylated H2A.Z. Fig. S2. Methylation activity of SMYD3 on histones in the context of nucleosome and evaluation of the H2A.ZK101me2 antibody. Fig. S3. Dimethylation of H2A.Z is critical for its protein interaction. Fig. S4. Dimethylation of H2A.Z is critical for promoting cell growth. Fig. S5. Genes affected by SMYD3 knockdown and H2A.ZK101Q expression. Fig. S6. Cyclin A1 is one of the downstream targets co-regulated by SMYD3 and H2A.ZK101me2.

It is crucial to address the following issues for ubiquitous robotics manipulation applications: (a) vision-based manipulation tasks require the robot to visually learn and understand the object with rich information like dense object descriptors; and (b) sim-to-real transfer in robotics aims to close the gap between simulated and real data. In this paper, we present Sim-to-Real Dense Object Nets (SRDONs), a dense object descriptors that not only understands the object via appropriate representation but also maps simulated and real data to a unified feature space with pixel consistency. We proposed an object-to-object matching method for image pairs from different scenes and different domains. This method helps reduce the effort of training data from real-world by taking advantage of public datasets, such as GraspNet. With sim-to-real object representation consistency, our SRDONs can serve as a building block for a variety of sim-to-real manipulation tasks. We demonstrate in experiments that pre-trained SRDONs significantly improve performances on unseen objects and unseen visual environments for various robotic tasks with zero real-world training.

Supplementary Table S1. List of methylated histone proteins identified from in vitro HMT assay on calf thymus extracts followed by LC-MS/MS analysis