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Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.
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BACKGROUND AND AIMS: Post-cholecystectomy biliary strictures can be treated surgically or nonsurgically. Although endoscopic or percutaneous treatments are the preferred approaches, these methods are not feasible in cases in which complete stricture occlusion prevents the successful passage of a guidewire. The utility of magnetic compression anastomosis (MCA) in patients with post-cholecystectomy complete biliary obstruction that cannot be treated conventionally was evaluated. METHODS: MCA was performed in 10 patients with post-cholecystectomy biliary strictures that did not resolve with conventional endoscopic or percutaneous treatment. One magnet was delivered through the percutaneous transhepatic biliary drainage tract, and another was advanced via ERCP of the common bile duct. After magnet approximation and recanalization, a fully covered self-expandable metal stent (FCSEMS) was placed for 3 months and then replaced for an additional 3 months. Stricture resolution was evaluated after FCSEMS removal. RESULTS: Among the 10 patients who underwent MCA for post-cholecystectomy biliary stricture, the biliary injury was Strasberg type B in 2, type C in 3, and type E in 5. Recanalization was successful in all patients (technical success rate, 100%). The mean follow-up period after recanalization was 50.2 months (range, 13.2-116.8 months). Partial restenosis after MCA occurred in 2 patients at 24.1 and 1.6 months after stent removal. ERCP with FCSEMS placement resolved the recurrent stenosis in both patients. CONCLUSIONS: MCA is a useful nonsurgical alternative treatment for complete biliary obstruction after cholecystectomy that cannot be resolved by use of conventional methods.
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Background: This study evaluated the effectiveness of short fully covered self-expanding metal stents (FCSEMS) with an anti-migration design in treating benign biliary strictures (BBS) not related to living donor liver transplantation (LDLT). Methods: A retrospective analysis was conducted on 75 patients who underwent FCSEMS insertion for BBS management. Stents were initially kept for 3 months and exchanged every 3 months until stricture resolution. Adverse events and stricture recurrence after FCSEMS removal were assessed during follow-up. Results: The study outcomes were technical success, stenosis resolution, and treatment failure. Technical success was 100%, with stricture resolution in 99% of patients. The mean onset time of BBS post-surgery was 4.4 years, with an average stent indwelling period of 5.5 months. Stricture recurrence occurred in 20% of patients, mostly approximately 18.8 months after stent removal. Early cholangitis and stent migration were noted in 3% and 4% of patients, respectively. Conclusions: This study concludes that short FCSEMS demonstrate high efficacy in the treatment of non-LDLT-related BBS, with a low incidence of interventions and complications. Although this is a single-center, retrospective study with a limited sample size, the findings provide preliminary evidence supporting the use of short FCSEMS as a primary treatment modality for BBS. To substantiate these findings, further research involving multicenter studies is recommended to provide additional validation and a broader perspective.
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Background: Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy. Methods: We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity. Results: A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression. Conclusion: PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.
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Neoplasias do Sistema Biliar , Receptor de Morte Celular Programada 1 , Humanos , Antígeno B7-H1/metabolismo , Neoplasias do Sistema Biliar/tratamento farmacológico , LigantesRESUMO
BACKGROUND AND AIMS: Propofol, a widely used sedative in GI endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultrashort-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study compared the safety and efficacy of remimazolam and propofol during EUS procedures. METHODS: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events (AEs) during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints were the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both endoscopists and patients. RESULTS: Four hundred patients enrolled in the study: 200 received remimazolam (10.8 ± 7.7 mg) and 200 received propofol (88.0 ± 49.1 mg). For cardiorespiratory AEs, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs 16%, P = .022). A nonsignificant trend was found toward less oxygen desaturation (1.0% vs 3.5%, P = .09), respiratory depression (.5% vs 1.5%, P = .62), hypotension (2.5% vs 5.5%, P = .12), and tachycardia (4.5% vs 5.5%, P = .68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients. CONCLUSIONS: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations. (Clinical trial registration number: KCT 0007643.).
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Benzodiazepinas , Endossonografia , Hipnóticos e Sedativos , Hipotensão , Propofol , Humanos , Propofol/efeitos adversos , Propofol/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/administração & dosagem , Hipotensão/induzido quimicamente , Idoso , Insuficiência Respiratória/induzido quimicamente , Satisfação do Paciente , Adulto , Taquicardia/induzido quimicamente , Período de Recuperação da AnestesiaRESUMO
BACKGROUND: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. METHODS: TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. RESULTS: Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001). CONCLUSION: TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.
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Neoplasias do Sistema Biliar , Proteínas dos Microfilamentos , Humanos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Linhagem Celular TumoralRESUMO
To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.
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Neoplasias Pancreáticas , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Metástase Linfática , Prognóstico , Neoplasias Pancreáticas/patologia , Quimioterapia Adjuvante , Biomarcadores , Recidiva Local de Neoplasia/patologiaRESUMO
INTRODUCTION: Pancreatic cancer cells generally accumulate large numbers of lipid droplets (LDs), which regulate lipid storage. To promote rapid diagnosis, an automatic pancreatic cancer cell recognition system based on a deep convolutional neural network was proposed in this study using quantitative images of LDs from stain-free cytologic samples by optical diffraction tomography. METHODS: We retrieved 3D refractive index tomograms and reconstructed 37 optical images of one cell. From the four cell lines, the obtained fields were separated into training and test datasets with 10,397 and 3,478 images, respectively. Furthermore, we adopted several machine learning techniques based on a single image-based prediction model to improve the performance of the computer-aided diagnostic system. RESULTS: Pancreatic cancer cells had a significantly lower total cell volume and dry mass than did normal pancreatic cells and were accompanied by greater numbers of lipid droplets (LDs). When evaluating multitask learning techniques utilizing the EfficientNet-b3 model through confusion matrices, the overall 2-category accuracy for cancer classification reached 96.7 %. Simultaneously, the overall 4-category accuracy for individual cell line classification achieved a high accuracy of 96.2 %. Furthermore, when we added the core techniques one by one, the overall performance of the proposed technique significantly improved, reaching an area under the curve (AUC) of 0.997 and an accuracy of 97.06 %. Finally, the AUC reached 0.998 through the ablation study with the score fusion technique. DISCUSSION: Our novel training strategy has significant potential for automating and promoting rapid recognition of pancreatic cancer cells. In the near future, deep learning-embedded medical devices will substitute laborious manual cytopathologic examinations for sustainable economic potential.
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Gotículas Lipídicas , Neoplasias Pancreáticas , Humanos , Redes Neurais de Computação , Aprendizado de Máquina , Neoplasias Pancreáticas/diagnóstico por imagem , TomografiaRESUMO
BACKGROUND: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. METHODS: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. RESULTS: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. CONCLUSIONS: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Transcriptoma , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Perfilação da Expressão Gênica , Prognóstico , Microambiente Tumoral/genética , Análise de Célula Única , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genéticaRESUMO
PURPOSE: Cannulation of the major papilla is the most challenging part of endoscopic retrograde cholangiopancreatography (ERCP) for which physician-controlled wire-guided cannulation (PCWGC) and assistant-controlled wire-guided cannulation (ACWGC) are used as the cannulation techniques. PCWGC can reportedly save up to about 30% of the labor cost by reducing the number of assistants. This study aims to compare the safety and efficacy of PCWGC and ACWGC. MATERIALS AND METHODS: Of the 2151 patients aged >20 years (4193 cases) who underwent ERCP at Yonsei University Medical Center between January 2015 and December 2016, 989 were included in this study. RESULTS: Among efficacy outcomes, cannulation success rate, rate of precut sphincterotomy (PCWGC vs. ACWGC: 21.3% vs. 25.9%), bile duct cannulation time (PCWGC vs. ACWGC: median 3.0 minutes vs. 3.6 minutes), and total procedure time (PCWGC vs. ACWGC: median 13.6 minutes vs. 13.1 minutes) were not significantly different. Among safety outcomes, lower rates of post-ERCP pancreatitis were observed with PCWGC than with ACWGC (PCWGC vs. ACWGC: 5.8% vs. 8.8%, p=0.128). Among other post-ERCP adverse events (bleeding, perforation, and cholangitis), the difference was not significant between the groups. Radiation exposure (total dose area product, PCWGC vs. ACWGC: median 1979.9 µGym² vs. 2062.0 µGym², p=0.194) and ERCP cost excluding labor cost (PCWGC vs. ACWGC: $1576 vs. $1547, p=0.606) were not significantly different. CONCLUSION: Requiring less assistants, PCWGC showed comparable efficacy and safety to ACWGC. PCWGC can be considered as an alternative option, especially in facilities lacking manpower and resources.