Search Results (730)

Background/Objectives: Treatment planning for stage III non–small cell lung cancer (NSCLC) presents dosimetric challenges due to the proximity of critical structures. RapidPlan (RP), a knowledge-based planning (KBP) system, offers the potential for improved plan consistency and organ-at-risk (OAR) sparing. The objective of this study was to compare dosimetric and clinical outcomes of RP-generated plans versus manually optimized plans in patients with stage III NSCLC undergoing IMRT or VMAT. Methods: In this retrospective analysis, 50 patients treated with concurrent chemoradiation for stage III NSCLC at Hadassah Medical Center (2015–2021) were analyzed. RP plans were generated using a lung-specific model in the Eclipse treatment planning system and compared with the original clinical manual plans. Dosimetric parameters for target volumes and OARs were evaluated, and subgroup analyses were performed by technique (IMRT vs. VMAT). Toxicity and survival outcomes were analyzed, and Normal Tissue Complication Probability (NTCP) modeling was conducted. Results: RP significantly reduced mean heart dose (Δ = −2.54 Gy, p < 0.001), spinal cord maximum dose (Δ = −4.08 Gy, p < 0.001), and esophageal mean dose (Δ = −3.89 Gy, p < 0.001) compared with manual plans. Lung doses were slightly higher in RP plans (V20 Δ = +2.12%, p < 0.001). VMAT-RP plans demonstrated greater cardiac and esophageal sparing than VMAT-manual plans. RP yielded significant NTCP reductions for the heart (0.34% → 0.20%) and esophagus (16.6% → 11.5%), but no improvement for lung or spinal cord. Lung toxicity ≥ grade 2 was associated with reduced overall survival (16.2 vs. 51.8 months, p < 0.001). Conclusions: RapidPlan-based knowledge-based planning enhances OAR sparing while maintaining target coverage in locally advanced NSCLC. Slight increases in lung dose highlight the need for ongoing model refinement. An association between lung toxicity and reduced survival was observed, underscoring the impact of treatment-related morbidity on outcomes. Full article

Esophageal squamous cell carcinoma (ESCC) remains a major global health challenge due to its aggressive nature and frequent late-stage diagnosis. Accurate locoregional staging is critical for guiding appropriate therapy, and endoscopic ultrasound (EUS) has emerged as the preferred modality for assessing tumor depth and regional lymph node involvement. In this narrative review, we provide a comprehensive overview of the role of EUS in the management of ESCC, from initial staging to post-treatment assessment. We discuss its strengths and limitations, particularly in differentiating early-stage disease and in restaging after neoadjuvant therapy. The importance of a multimodal approach—integrating EUS with computed tomography (CT), positron emission tomography (PET), and histologic sampling—is emphasized to improve diagnostic precision. We also explore emerging techniques, such as contrast-enhanced EUS, elastography, and novel therapeutic strategies including immune checkpoint inhibitors and endoscopic mucosal resurfacing. While EUS remains a cornerstone in the management of ESCC, ongoing innovation and integration with personalized medicine are expected to further enhance its clinical impact. Full article

A 3-year-old West Highland White Terrier presented to our hospital with dyspnea following aspiration of barium contrast medium during diagnostic imaging for a suspected esophageal foreign body (day 0). Barium contrast radiography had revealed a foreign body in the lower esophagus. During anesthesia, the patient regurgitated and developed respiratory failure and cyanosis. Despite immediate intubation, suction, and ventilatory management, respiratory parameters remained poor. Respiratory support with extracorporeal membrane oxygenation (ECMO) enabled control of blood gas parameters, and tracheobronchial lavage with temporary complete airway occlusion was performed. ECMO was withdrawn once the respiratory status normalized (total support time: 3 h). Considering the possibility of hypoxia-induced brain damage, the patient was extubated on day 1. The dog was alert, changed positions, and drank water independently 5 h after extubation. However, neurological symptoms were observed 1 h later. Cranial magnetic resonance imaging was performed on day 6 owing to persistent neurological symptoms. Although no ECMO-related complications, such as cerebral infarction, hemorrhage, or herniation, were observed, the white matter exhibited hyposignal, indicating hypoxic encephalopathy. The patient died on day 8, without improvement in neurological symptoms. ECMO is an effective treatment option for dogs with respiratory failure, and its prompt introduction may improve survival. Full article

The curative management of localized esophageal and esophagogastric junction (EGJ) cancers has undergone major changes over the past decade, shaped by multimodal strategies integrating chemotherapy, chemoradiotherapy, surgery, and more recently, immunotherapy. For esophageal squamous cell carcinoma (SCC), neoadjuvant or definitive chemoradiotherapy remains the standard of care in Western countries. In contrast, for adenocarcinoma (AC) of the esophagus and EGJ, perioperative chemotherapy has emerged as the preferred strategy. Despite these advances, long-term outcomes remain suboptimal, and recurrence continues to pose a major challenge, highlighting the need to optimize patient selection and treatment sequencing. The integration of immunotherapy in the perioperative or adjuvant setting has recently led to improvements in surrogate endpoints yet overall survival benefit remains under investigation. For patients with tumors harboring microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), checkpoint inhibitors show exceptional activity, and non-operative management may be feasible in select cases. Conversely, human epidermal growth receptor 2 (HER2)-targeted strategies, although effective in metastatic disease, have not yet translated into practice-changing benefit in the curative setting. The role of circulating tumor deoxyribo nucleic acid (DNA) and functional imaging as real-time tools to assess response and guide treatment adaptation is also being actively explored. This review provides a comprehensive overview of current standards, ongoing developments, and future directions for the treatment of localized esophageal and EGJ cancers, with a focus on emerging personalization strategies and biomarker-driven approaches aimed at improving cure rates and minimizing treatment-related morbidity. Full article

Genetic abnormalities of the fibroblast growth factor receptor 2 (FGFR2) gene, including amplification, fusions, and mutations, have been reported in various solid tumors. While molecular targeted therapies against FGFR2 fusion have been proved to be useful in cholangiocarcinoma, the therapeutic significance of FGFR2 inhibitors remains unclear in other various solid cancers. Genomic and clinical information from solid tumor cancer gene panel testing cases is consolidated in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. This study aimed to utilize the C-CAT database to clarify the clinical–pathological significance of FGFR2 abnormalities. A total of 101,231 patients with solid cancer have been registered in the C-CAT database between June 2019 and June 2025. Of the 101,231 cases, 1312 cases with FGFR2 gene abnormalities were analyzed. FGFR2 alterations included amplification in 515 cases, fusion in 280 cases, and mutations in 568 cases. They were detected most frequently in the biliary tract (271 cases), esophagus/stomach (231 cases), and breast (211 cases). Amplification was frequent in the esophagus/stomach (205 cases) and breast (105 cases). Mutations were frequent in the uterus (111 cases), breast (89 cases), and biliary tract (86 cases). Among 515 FGFR2 alteration cases, FGFR2 inhibitors were administered in 85 cases. Of the 85 cases, disease control was achieved in 49 cases, 44 cases of which were biliary tract cancer. FGFR2 might be a promising therapeutic target not only for cholangiocarcinoma with fusion but also for esophagus/stomach cancer and breast cancer with FGFR2 alterations. Full article

Background and Clinical Significance: Barrett’s esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Accurately predicting which patients with BE are at the highest risk of progressing to EAC is a significant clinical challenge. This article discusses how the tissue systems pathology test (TSP-9, TissueCypher) can help guide risk-aligned care for patients with BE. TSP-9 is an AI-driven prognostic test that stratifies patients with BE for risk of progression to high-grade dysplasia (HGD)/EAC. Case Report Presentation: Three clinically low-risk patients had esophageal biopsies tested by TSP-9. The real-world utility of TSP-9 is demonstrated through a brief discussion of how the test was utilized to assess each patient’s personalized risk of BE progression to HGD/EAC and inform risk-aligned care. Conclusions: The use of validated AI-powered tools such as TSP-9 is poised to become standard practice in gastroenterology clinical settings and will help improve health outcomes for patients with BE to prevent EAC-related mortality. Full article

Candida spp. are common components of normal microbiota in the oral cavity. However, Candida albicans can be a primary cause of superficial infections in the oral cavity and esophagus, especially in immunocompromised individuals. While these infections are rarely life-threatening, they can significantly impair quality of life and, in severe cases, progress to hematogenous dissemination. Oral candidiasis often exhibits as pseudomembranous, erythematous (atrophic), chronic hyperplastic, denture stomatitis, or angular cheilitis. Esophageal candidiasis is typically diagnosed by upper endoscopy, which involves histological examination and brushing. Clinical guidelines recommend topical antifungal agents for mild oral candidiasis, and systemic agents for moderate-to-severe disease or when topical therapy fails. However, azole antifungals pose a substantial risk of drug–drug interactions, primarily due to the inhibition of cytochrome P450 enzymes and drug transporters, which dramatically alters the pharmacokinetics of co-administered drugs. Additionally, amphotericin B, a polyene macrolide antibiotic, may cause nephrotoxicity and electrolyte disturbances (e.g., hypokalemia and hypomagnesemia). Moreover, the co-administration of nephrotoxic drugs may augment the toxicity associated with amphotericin B. Therefore, this review aimed to provide a comprehensive overview of the management of oral and esophageal candidiasis from the viewpoint of clinical pharmacology, with a particular focus on drug–drug interactions and adverse effect profiles. Full article

Several major cancer types exhibit significant sex dimorphism in incidence and survival. Whether and how sex as a biological factor impacts tumorigenesis, progression, and survival warrants full investigation, as such knowledge may lead to novel, precise prevention and treatment strategies. We reviewed epidemiological and molecular data on sex differences in cancers of the esophagus, bladder, head and neck, lung, liver, kidney, stomach, and skin melanoma, as well as the potential role of androgens and androgen receptor (AR) activity in these cancers. The potential molecular mechanisms are briefly discussed. Elevated testosterone (T) levels seemed to be associated with increased liver cancer and cutaneous melanoma incidences, and with reduced esophageal cancer risk. AR activity does not always correlate with T levels in tumorigenesis and progression. Higher AR expressions are associated with poorer survival in ESCC, whereas the role of AR in the survival of HNSCC and melanoma patients is inconsistent. The molecular impact of AR in liver cancer, kidney cancer, melanoma, and lung cancer is controversial. However, AR is likely to promote tumor growth and/or progression in esophagus, bladder, head and neck, and stomach cancers, and thus is associated with poor survival. Patients diagnosed with a tumor in this latter group could potentially benefit from therapeutic approaches targeting AR. Overall, the research on sex hormone androgens and AR in these cancers is limited. Further research is needed to determine a possible U-shaped relationship of T with cancer risk, and to decipher the role of testosterone and AR in some of these tumors to facilitate our understanding of sex dimorphism and to explore novel T/AR-based treatment options. Full article

Background: Dysphagia is a common problem in older adults, characterized as a swallowing disorder that prevents food from passing from the mouth to the esophagus. Besides impairing dietary intake and leading to malnutrition, dysphagia also severely restricts water intake. Purpose: This study aimed to develop polysaccharide-based hydrogels as dysphagia-friendly finger foods designed to provide high water content and enable controlled vitamin delivery to older persons with dysphagia. Procedures: Agar–carboxymethylcellulose (Agar-CMC) composite hydrogels with incorporated vitamins C, B₉, B, and D₃ were developed and tested for their textural and rheological properties, vitamin stability during storage, and vitamin release under simulated gastrointestinal conditions. Finally, a fiberoptic endoscopic swallowing assessment and sensory evaluation were conducted. Main Findings: Increasing the agar concentration in Agar-CMC hydrogels improved their internal structure and handling properties as finger foods, while still being easily breakable during swallowing. Agar-CMC hydrogels’ structure protected vitamins during processing and six weeks of storage. Vitamin release started immediately and remained steady in the gastric phase, with a noticeable increase at the beginning of the intestinal phase, resulting in 70–100% vitamin release by the end of this phase. The Fiberoptic Endoscopic Swallowing Evaluation confirmed their suitability for individuals with mild to moderate oropharyngeal dysphagia, with a low risk of aspiration (1 point on the Penetration-Aspiration Scale out of 8). Principal Conclusions: The developed Agar-CMC hydrogels present a promising dysphagia-friendly finger food alternative with high water content. They effectively deliver essential vitamins throughout the gastrointestinal tract, and notably demonstrate a low aspiration risk, making them suitable for individuals with mild to moderate oropharyngeal dysphagia. Full article

Optical imaging technologies expand gastrointestinal endoscopy beyond white-light endoscopy (WLE), improving visualization of mucosal, vascular, and subsurface features. They are applied to the detection of neoplastic and premalignant lesions, inflammatory diseases, and small bowel and pancreatic disorders, though their validation and readiness for routine practice vary. This review critically evaluates both guideline-endorsed and investigational optical imaging techniques across major gastrointestinal indications, highlighting diagnostic performance, level of validation, current guideline recommendations, and practical challenges to adoption. In Barrett’s esophagus, narrow-band imaging (NBI) is guideline-endorsed, while acetic acid chromoendoscopy is validated in expert centers. For gastric intestinal metaplasia and early gastric cancer, magnifying NBI achieves diagnostic accuracies exceeding 90% and is guideline-recommended, with acetic acid chromoendoscopy aiding in margin delineation. In inflammatory bowel disease, dye-spray chromoendoscopy is the reference standard for dysplasia surveillance, with virtual methods such as NBI, FICE, and i-SCAN serving as practical alternatives when dye application is not feasible. In the colorectum, NBI supports validated optical diagnosis strategies (resect-and-discard, diagnose-and-leave), while dye-based chromoendoscopy improves detection of flat and serrated lesions. Capsule endoscopy remains the standard for small bowel evaluation of bleeding, Crohn’s disease, and tumors, with virtual enhancement, intelligent chromo capsule endoscopy, and AI-assisted interpretation emerging as promising adjuncts. Pancreaticobiliary applications of optical imaging are also advancing, though current evidence is still preliminary. Investigational modalities including confocal laser endomicroscopy, optical coherence tomography, autofluorescence, Raman spectroscopy, and fluorescence molecular imaging show potential but remain largely restricted to research or expert settings. Guideline-backed modalities such as NBI and dye-based chromoendoscopy are established for clinical practice and supported by robust evidence, whereas advanced techniques remain investigational. Future directions will rely on broader validation, integration of artificial intelligence, and adoption of molecularly targeted probes and next-generation capsule technologies, which together may enhance accuracy, efficiency, and standardization in gastrointestinal endoscopy. Full article

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory disorder that causes progressive ossification and fusion of the spine, particularly in the cervical region. This results in a rigid spinal column that is highly susceptible to unstable fractures, even after low-energy trauma. Cervical fractures in AS are often complex, extending through multiple spinal segments, and are associated with a high risk of neurological compromise. Esophageal injury associated with such fractures is rare but clinically significant, as the anatomical vicinity of the esophagus makes it vulnerable to direct trauma, delayed perforation, or secondary damage from fracture displacement and hardware failure. Aim: The purpose of this review is to present and highlight the clinical relevance of esophageal injury in cervical spine trauma among patients with AS, emphasizing the diagnostic challenges and surgical treatment in order to improve outcomes. Results: Esophageal injuries in the context of AS-related cervical trauma are frequently overlooked due to subtle clinical manifestations such as dysphagia, subcutaneous emphysema, or covert signs of mediastinitis. Plain radiographs are insufficient to identify such complications; advanced imaging modalities are often required for detection. Management is complex and usually demands a multidisciplinary approach, involving both stabilization of the cervical spine and repair of the esophagus. Despite treatment efforts, these patients remain at increased risk for morbidity and mortality, mainly due to infection and sepsis. Conclusions: Esophageal injury in cervical spine trauma associated with AS is an uncommon but life-threatening condition. Early recognition, comprehensive radiologic evaluation, and careful surgical planning are crucial for optimal management. Heightened clinical suspicion and awareness of this rare complication are essential to improve diagnostic accuracy and patient outcomes. Full article

Background: Head and neck cancers (HNCs) represent a substantial global health burden, with an estimated mortality rate exceeding 50% annually. Among the various subsites, pharyngeal and laryngeal carcinomas are recognized as two of the most aggressive and challenging forms, characterized by high incidence, poor prognosis, and a strong association with advanced-stage diagnosis. Methods: A systematic literature review was performed using electronic literature databases (e.g., PubMed, Google Scholar). Search terms included “head and neck cancer”, “laryngeal cancer”, and “pharyngeal cancer”. Selected studies are published within the last two decades. Results: Laryngeal cancer constitutes approximately 40% of head and neck malignancies, with a clear male predominance, and pharyngeal cancer shows increased incidence in male populations from the Americas and Africa. Despite therapeutic advancements in radiotherapy, chemotherapy, and immunotherapy, overall survival rates remain unsatisfactory. Moreover, patients are at increased risk for second primary malignancies, particularly within the lungs and esophagus, due to the widespread carcinogenic exposure along the aerodigestive tract. Conclusions: To mitigate the morbidity and mortality associated with pharyngeal and laryngeal cancers, early detection, risk factor mitigation, and public health education are imperative. Enhancing screening among high-risk populations and adopting personalized, multidisciplinary treatment strategies may significantly improve clinical outcomes and long-term survival. Full article

Background/Objectives: Postoperative pneumonia and other infectious complications after robotic-assisted minimally invasive esophagectomy still contribute to morbidity and mortality. Selective oral decontamination of the esophagus prior to surgery might reduce the rate of infectious complications. However, its impact on the esophageal microbiota is unknown. Therefore, this study aimed to analyze whether selective oral decontamination of the esophagus prior to surgery reduces postoperative pneumonia rates and alters the esophageal microbiome. Methods: We conducted a proof-of-principle study including 22 patients who underwent robotic-assisted minimally invasive esophagectomy. Thirteen patients were treated with 50 mg amphotericin B, 8 mg tobramycin, and 10 mg colistin orally 7 days prior to surgery, intraoperatively, and 5 days postoperatively. The remaining nine patients received standard-of-care treatment (no oral decontamination). The esophageal microbiome was assessed using 16S rRNA gene amplicon libraries which were annotated using the Ribosomal Data Project. The incidence of postoperative (at discharge from hospital or 30 days, whichever was later) infectious complications was assessed. Results: Selective oral decontamination was associated with reduced overall rates of infectious complications (7.7% vs. 55.5%, p = 0.008) and postoperative pneumonia (0% vs. 33.3%, p = 0.007). Alterations in the esophageal microbiome depending on selective oral decontamination were detectable. The microbiomes of patients with infectious complications showed higher abundances of Neisseria and lower abundances of Streptococcus than samples without infectious complications. Conclusions: Selective oral decontamination reduced the rate of postoperative complications, postoperative pneumonia in particular, after robot-assisted esophagectomy. Alterations in the microbiome were also evident following decontamination. Further studies with larger sample sizes are necessary to confirm these data. Full article

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease of the esophagus within the type 2 inflammatory spectrum, characterized by progressive tissue remodeling driven by uncontrolled inflammation. Its incidence and prevalence are rising sharply, likely reflecting environmental triggers acting on genetic and epigenetic susceptibility. Therapeutic options have expanded rapidly, with recent approvals of new topical steroidal formulations together with biologic compounds. Proton pump inhibitors (PPIs), older swallowed topical corticosteroid (STC), and dietary interventions remain in use but are limited by suboptimal adherence and treatment discontinuation. This has driven a shift toward advanced orally dispersible STCs formulations—most notably budesonide orally dispersible tablets (BOT), budesonide oral suspension (BOS), and fluticasone orally dispersible tablets (FOT). BOT, the most extensively studied, achieves high rates of histologic and clinical remission, with favorable safety and superior adherence compared to earlier STCs formulations. This comprehensive overview focuses on following key research findings and novelty aspects of new treatments: (a) optimized esophageal targeting through orally dispersible or viscous formulations of STC, enhancing mucosal contact time and improving drug delivery to affected tissues compared to older formulations; (b) robust evidence for both induction and maintenance rates of remission, with data extending up to nearly 2 years and showing stable efficacy across clinical, histologic, and endoscopic endpoints; (c) effectiveness in STC-refractory patients, with BOT showing benefit even in those previously unresponsive to older STC formulations. This review synthesizes evidence of steroid therapy in EoE, from pharmacological aspects to clinical efficacy from randomized trials and emerging real-world studies, highlighting its impact on EoE management and outlining future therapeutic directions. Full article

Aerodigestive fistulas represent a major challenge in clinical practice. This problem is burdened with severe morbidity and mortality, despite recent advantages in endoscopic endoluminal repair techniques. Special problems are fistulas localized higher, engaging the proximal esophagus and trachea, which in adults most often result from post-intubation injury. Surgery is generally demanding and reserved for the patients in whom other, less invasive options fail. Hereby, we present a case of post-intubation tracheoesophageal fistula, successfully treated with endoscopic vascular plug placement. Full article