Cholangiocarcinoma (CCA) is a primary malignant tumor originating from the epithelium of the bile duct mucosa. It is the second most common primary tumor of the liver and biliary tract. Based on tumor location, CCA is classified as intrahepatic and extrahepatic. Clinical diagnosis relies on imaging techniques (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI]), while the final diagnosis is confirmed through histopathological examination of biopsy, brush swab, or post-operative samples. Imaging plays a critical role in diagnosing, staging, and guiding the treatment of biliary cancers. Key imaging methods include magnetic resonance cholangiopancreatography (MRI with MRCP), endoscopic retrograde cholangiopancreatography, endoscopic ultrasound (EUS), and positron emission tomography (PET). Selecting the most suitable diagnostic tool is challenging due to the distinct properties of each method, which are tailored to different diseases and stages of diagnosis or treatment. For example, MRCP provides superior visualization of biliary tract narrowing/dilatation compared to direct cholangiography (ERC) and is more effective in assessing tumor extent. Ultrasound is useful for initial evaluation of bile duct and gallbladder tumors and for identifying bile duct dilatation. CT is effective for detecting focal lesions and staging cancer progression, while MRI is considered the gold standard for tumor visualization. EUS offers a detailed assessment of extrahepatic bile ducts, gallbladder, hepatic hilar structures, local lymph nodes, and vessels. Although ERC allows biopsy or smear collection, it does not assess tumor extent. PET is valuable for detecting distant metastases, monitoring treatment efficacy, and evaluating recurrence. This review focuses on the role of various imaging techniques in the diagnosis, staging, treatment response prediction, and therapy of CCA.
Concurrent chemoradiotherapy (CCRT) involves the simultaneous administration of chemotherapy and radiotherapy, in which low-dose chemotherapy enhances the effectiveness of radiotherapy. This combined approach mitigates tumor recurrence and metastasis, ultimately improving patient prognosis. The primary mechanism behind the increased radiosensitivity induced by concurrent chemotherapy involves inhibiting tumor cell repair and the complementary effects of chemotherapy and radiotherapy on different phases of the cell cycle. Despite CCRT application in patients with locally advanced cervical cancer (LACC), the 5-year survival rate remains at 60%. To improve treatment efficacy, a series of exploratory investigations have been conducted, encompassing the integration of targeted therapy, immunotherapy, and utilization of immunomodulatory agents in neoadjuvant protocols preceding CCRT. Although targeted therapies and immunomodulators represent efficacious interventions for LACC management, the scarcity of robust, large-scale evidencebased data necessitates the undertaking of multicenter prospective randomized Phase III clinical trials and dissemination of high-quality publications to elevate the standard of evidence-based medicine. This consensus acts as a valuable resource for clinicians and researchers, highlighting recent seminal evidence-based studies and the evolving landscape of clinical research on targeted and immunomodulatory agents.
Immune checkpoint inhibitors (ICIs) have shown promise in treating triplenegative breast cancer (TNBC), but resistance to these therapies remains a significant challenge. AT-rich interactive domain 1A (ARID1A), a component of the SWItch/Sucrose Non-Fermentable chromatin remodeling complex, is frequently mutated in TNBC and is associated with increased programmed cell death ligand 1 expression, which contributes to immune evasion. Paradoxically, this mutation may make TNBC potentially more responsive to ICIs. Chromatin-mediated gene expression requires a balance between ARID1A and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, and ARID1A deficiency results in enhanced EZH2 activity, contributing to various oncologic processes. Epigenetic modulation through EZH2 inhibition could exploit the synthetic lethality between ARID1A deficiency and EZH2 activity, which may reduce the immunosuppressive tumor microenvironment and enhance infiltration and activity of cytotoxic T-cells within the tumor, thereby synergizing with immune checkpoint inhibition. This review explores the potential of EZH2 inhibition as a therapeutic strategy to overcome immune checkpoint resistance in ARID1A-deficient TNBC. In addition, the role of ARID1A deficiency as a radiosensitizer is also discussed in the context of combination therapy strategies.
Previously, we demonstrated that the pan-immune-inflammation value (PIV) and pretreatment tooth extraction (TE) were independent predictors of osteoradionecrosis of the jaws (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) undergoing concurrent chemoradiotherapy (C-CRT). This study aimed to determine if combining PIV and TE, termed the PIV-TE-ORNJ index, and could improve the prediction of ORNJ prevalence in the same scenario. We divided patients into two groups based on each factor, with the PIV and TE cutoffs at 833 and 4, respectively, as determined in our previous study. The novel PIV-TE-ORNJ index, which combined these factors, revealed four probable groups: Group 1, PIV < 833 and TE < 4; Group 2, PIV < 833 but TE ≥ 4; Group 3, TE < 4 but PIV ≥ 833; and Group 4, PIV ≥ 833 and TE ≥ 4. The medical records of 220 patients with LA-NPC were reviewed retrospectively. Comparisons between four groups revealed that the ORNJ rates for Groups 1 - 4 were 1.1%, 6.6%, 6.1%, and 43.8%, respectively (P < 0.001). Because the ORNJ rates in Groups 2 and 3 were interchangeable (P = 0.91), these groups were merged, and a three-tiered novel PIV-TE-ORNJ index was created: low risk, PIV < 833 and TE < 4; intermediate risk, PIV < 833 but TE ≥ 4, or TE < 4 but PIV ≥ 833; and high risk, PIV ≥ 833 and TE ≥ 4. Comparisons between the three groups demonstrated that the low- and high-risk groups had the lowest (1.1%) and highest (43.8%) ORNJ rates, respectively, whereas the ORNJ rate of the intermediate-risk group was in between (6.4%) (P < 0.001 for each). The PIV-TE-ORNJ index successfully stratified patients with LA-NPC into low-, intermediate-, and high-risk groups after C-CRT.
Radiation-induced skin injury (RISI) is a frequent complication of radiotherapy that can severely hinder treatment and endanger patients’ lives. Current treatments offer limited efficacy in reducing symptoms. This study explores the protective effect of aspirin (ASP) on RISI and its underlying mechanisms. As in vivo RISI models, 8 - 12-week-old C57BL/6 mice were irradiated with a single dose of 20 Gy X-rays to the skin of the right thigh, with sham-irradiated mice serving as controls. ASP was administered orally for 7 days before irradiation. Skin samples were collected on day 14 post-irradiation for single-cell RNA sequencing (sc-RNAseq). RISI severity was assessed daily using a modified RTOG/EORTC scoring system (scores ranging from 1 to 5.5). Our results showed that ASP delayed the onset of RISI and reduced its severity. The sc-RNAseq revealed an increased number of interfollicular epidermal cycling (IFE C) cells in irradiated skin, with some cells showing G2M cell cycle arrest. These IFE C cells exhibited elevated expression of stemness markers, indicating their importance in both RISI damage and subsequent repair. The ASP-treated group showed delayed skin injury onset and reduced peak severity compared to untreated controls. Furthermore, ASP appeared to promote homologous recombination repair of radiation-induced DNA damage, contributing to its protective effect. In conclusion, IFE C cells undergo G2M arrest to repair radiation-induced damage. ASP shows potential in preventing RISI, possibly through enhancing DNA repair. These findings suggest a novel therapeutic role for ASP in mitigating RISI.
This study presents the first report on the fundamental dosimetric characterization of a novel image-guided radiosurgery system - the ZND-A Smart Knife (CNCI Co., Ltd, Xi’an, China). The dosimetric performance of this radiosurgery system was evaluated based on key parameters, including positioning reference point deviation, nominal focal point dose rate, focusing field size, dose gradient, and comprehensive error in dose calculation. The system employs “triple rotating and focusing” technique, and its dosimetric characteristics were measured. The maximum positioning reference point deviation for collimator #1 - 4 was 0.38 mm; the corresponding dose gradients were 3.1 mm, 3.4 mm, 5.4 mm, and 7.7 mm, respectively. In dose calculation, the maximum isocenter point dose deviation was 3.3%, and the area overlap ratio for the largest collimator (#4) reached 98.3%. These results demonstrate excellent dosimetric performance and clinical potential, confirming the safety and precision of the next-generation cone beam-focused gamma knife system.
Combinatorial chemoimmunotherapy has emerged as a potent approach in cancer treatment, offering the advantages of combining two treatment strategies (i.e., chemotherapy and immunotherapy), thereby reducing drug dosages and improving therapeutic outcomes. Nanomaterial-assisted drug delivery systems have garnered significant attention in chemoimmunotherapy for encapsulating and delivering therapeutic agents, as they can simultaneously target both cancer and immune cells, promoting drug accumulation with excellent therapeutic efficacy and minimal toxic side effects. This mini-review focuses on various aspects of immunotherapy and chemoimmunotherapy in cancer treatment and discusses several nanomaterialassisted drug delivery systems used in chemoimmunotherapy.
This study aimed to review 18fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG PET/CT) imaging characteristics of B-cell non-Hodgkin’s lymphoma (NHL) at Hanoi Oncology Hospital. PET/CT helps accurately assess the NHL stage compared with other diagnostic imaging methods, such as CT and magnetic resonance imaging. In this retrospective descriptive study, 86 newly diagnosed B-cell NHL cases were histopathologically and immunohistochemically examined at Hanoi Oncology Hospital between January 2018 and December 2022. Patients underwent 18FDG PET/CT for pretreatment staging. The stages before and after PET/CT were evaluated and compared. Before PET/CT, 26 (30.2%), 29 (33.7%), 15 (17.5%), and 16 (18.6%) patients were in stages I, II, III, and IV, respectively. After PET/CT, the rates of Stage I, II, III, and IV cases were 22.1%, 26.8%, 20.9%, and 30.2%, respectively. PET/CT results increased the stage in 21/86 patients (24.4%). The proportion of patients with advanced stages after PET/CT in the rapidly progressing histopathology group was higher (25%) than the slowly progressing histopathology group (21.4%), and the difference was not significant. Therefore, PET/CT is critical for accurately determining the disease stage of B-cell NHL, thereby helping to detect additional lesions missed by conventional imaging diagnostic tools.
We present two cases of chronic hemodialysis patients with suspicious lytic pelvic bone lesions in the context of secondary hyperparathyroidism (HPT). Bone biopsies were inconclusive. 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) scans revealed highly hypermetabolic lytic lacunar bone lesions scattered throughout the skeleton. Pathological 99mTc-hexakismethoxy- isobutyl-isonitrile (99mTc-MIBI) uptake in the cervical region suggested parathyroid tissue involvement, while whole-body 99mTc-MIBI scintigraphy did not reveal pathological uptake. Brown tumors were strongly suspected based on clinical and laboratory evidence of HPT, ruling out malignancy. Our cases suggest the superior sensitivity of 18F-FDG PET/CT in detecting and characterizing brown tumors compared to whole-body 99mTc-MIBI scintigraphy. This examination offers crucial insights into characterizing brown tumors based on morpho-metabolic criteria, minimizing inaccurate diagnosis of this pathological condition.
Positron emission tomography integrated with computed tomography using 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG PET/CT) plays a critical role in the localization, diagnosis, and management of infectious diseases and inflammatory disorders. This hybrid imaging modality provides morpho-metabolic information that aids in defining the etiology of unexplained inflammatory syndromes and assessing treatment response. A key advantage of 18F-FDG PET/CT is its ability to provide a comprehensive, “all in one” diagnostic solution, particularly in cases where localizing symptoms are absent, facilitating the identification of metastatic and/or septic foci. Recently, there has been increasing recognition among clinicians of its potential in diagnosing, characterizing, and assessing inflammatory disorders. This study evaluates the clinical utility of 18F-FDG PET/CT in identifying the etiology of inflammatory syndromes by analyzing 25 patients with unexplained inflammatory disorders. The findings highlight the high reproducibility, sensitivity, and specificity of this imaging modality in this context.