A combined nomogram based on radiomics and hematology to predict the pathological complete response of neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. METHODS: We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). RESULTS: We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819-0.928) and 0.772 (95% CI: 0.699-0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P < 0.05). A combined nomogram was constructed from these factors, and AUC reached 0.934 (95% CI: 0.896-0.972). DCA demonstrated that the clinical benefits brought by the nomogram for patients across an extensive range were greater than those of other individual models. CONCLUSIONS: By combining CT radiomics, hematological factors, and clinicopathological characteristics before treatment, we developed a nomogram model that effectively predicted whether ESCC patients would achieve pCR after nICT, thus identifying patients who are sensitive to nICT and assisting in clinical treatment decision-making.

Ultrasound elasticity of diamond at gigapascal pressures.

Diamond is the hardest known material in nature and features a wide spectrum of industrial and scientific applications. The key to diamond's outstanding properties is its elasticity, which is associated with its exceptional hardness, shear strength, and incompressibility. Despite many theoretical works, direct measurements of elastic properties are limited to only ∼1.4 kilobar (kb) pressure. Here, we report ultrasonic interferometry measurements of elasticity of void-free diamond powder in a multianvil press from 1 atmosphere up to 12.1 gigapascal (GPa). We obtained high-accuracy bulk modulus of diamond as K0 = 439.2(9) GPa, K0' = 3.6(1), and shear modulus as G0 = 533(3) GPa, G0' = 2.3(3), which are consistent with our first-principles simulation. In contrast to the previous experiment of isothermal equation of state, the K0' obtained in this work is evidently greater, indicating that the diamond is not fully described by the "n-m" Mie-Grüneisen model. The structural and elastic properties measured in this work may provide a robust primary pressure scale in extensive pressure ranges.

Expanded field of view frequency-selective incoherent holography by using a triple-beam setup.

We propose a new, to the best of our knowledge, method of incoherent optical frequency selection called three-pack frequency-selective incoherent holography. Compressed holography is reconstructed using phase shift intercepts and spatial transfer function convolution in the form of separation without loss of magnification or resolution. The frequency-selective reconstruction process removes the conjugate and DC terms along with the interception of the object wave. This work attempts three-dimensional reconstruction and selected-frequency phase extraction of axial slices in submicron steps, and the experimental results show the potential of the proposed method in areas such as compressed holography, extended field of view, and slice tomography.

Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo.

OBJECTIVES: Ferroptosis is associated with multiple inflammatory diseases. Periodontitis is an inflammatory disease mainly caused by oral opportunistic pathogens. However, the ferroptosis-periodontitis relationship has not been thoroughly described. We here analyzed whether ferroptosis is involved in periodontitis. MATERIALS AND METHODS: Human gingival fibroblasts (HGFs) were stimulated with P. gingivalis-LPS and ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and changes in mitochondrial morphology, ferroptosis-related factors, and inflammation levels were detected. After the rat experimental periodontitis model was established, changes in ferroptosis-related factors and inflammation levels were re-evaluated in the same manner. RESULTS: Porphyromonas gingivalis-LPS-induced mitochondrial shrinkage, an increase in mitochondrial membrane density, and upregulation of reactive oxygen species in HGFs. The expression of prostaglandin-endoperoxide synthase 2, transferrin receptor 1, and malondialdehyde and inflammation levels were upregulated, whereas the expression of solute carrier family seven member 11, glutathione peroxidase 4, superoxide dismutase, and glutathione were downregulated. Fer-1 attenuated these aforementioned changes and inflammation levels induced by P. gingivalis-LPS. The in vivo experiment results were consistent with the in vitro experiment results. CONCLUSIONS: Ferroptosis is involved in inflammatory processes in HGFs upon P. gingivalis-LPS stimulation. Ferroptosis is observed in the gingival tissue of periodontitis rats.

Effects of starter feeding and early weaning on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of lambs from birth to eighty-four days of age.

The early weaning and starter feeding have significant effects on lamb growth and digestive tract development. However, it is not clear whether the expression of IGF-1/IGF-1R genes could be affected by feeding starter and weaning. Therefore, a total of 102 Hu male neonatal lambs were randomly divided into 3 groups: fed with starter at 42d + weaned at 56d (group A), fed with starter at 7d + weaned at 28d (group B) and fed with starter at 7d + weaned at 56d (group C), to explore the effects of starter feeding and weaning age on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of Hu sheep. The results showed that IGF-I and IGF-IR genes were expressed extensively in various tissues of lambs, the expression of IGF-I was significantly higher in liver (p < 0.01), while the expression of IGF-IR was higher in rumen among gastrointestinal tissues. The mRNA level of IGF-I of group C was strikingly higher than that of group A at 28, 70, and 84d (p < 0.01) in liver, respectively. Rumen mRNA level of IGF-IR of group C was prominently higher than that of group A at 70d and 84d (p < 0.05), respectively. However, IGF-IR expression of group A was higher than that of group C at 14 and 42d (p < 0.05). The mRNA level of IGF-I of group B was significantly higher than that of group C at 42, 56, 70, and 84d (p < 0.01) in liver, while IGF-IR expression of group B was higher than that of group C at 70d (p < 0.01). In conclusion, early weaning and starter feeding affected liver IGF-I mRNA and rumen IGF-IR mRNA expression.

Docosahexaenoic Acid-Loaded Nanostructured Lipid Carriers for the Treatment of Peri-Implantitis in Rats.

Being the most common cause of implant failure, peri-implantitis is defined as a pathological condition associated with the occurrence of peri-implant plaque, characterized by peri-implant mucosal inflammation and progressive loss of the supporting bone tissue attributed to the persistence of pro-inflammatory cytokines. Docosahexaenoic acid (DHA), which is a type of omega-3 polyunsaturated fatty acid, is generally used for the treatment of many inflammatory diseases. However, a suitable form for dosing and its therapeutic effect on peri-implantitis remain unclear. In this study, a novel nanostructured lipid carrier (NLC) loaded with squalene and DHA was fabricated (DHA-loaded NLC). The encapsulation efficiency and drug loading efficiency values of the DHA-loaded NLC were 78.13% ± 1.85% and 28.09% ± 0.48%, respectively. The release of DHA was gradual and steady until 144 h. In addition, the free-radical-scavenging rate of DHA-loaded NLC (0.57 ± 0.03) was much higher than that of sole DHA (0.17 ± 0.003). By inhibiting nuclear factor-κB p65 nuclear translocation, DHA-loaded NLC prevented the activation of nuclear factor-κB downstream inflammatory pathways and exerted anti-inflammatory effects on macrophages. Moreover, DHA-loaded NLC showed better effects on preventing alveolar bone resorption of rat peri-implantitis model than sole DHA. Hence, DHA-loaded NLC enhanced the anti-inflammatory bioavailability of DHA, offering a novel approach for the treatment of peri-implantitis.

[Research progress on the identification of central lung cancer and atelectasis using multimodal imaging].

Central lung cancer is a common disease in clinic which usually occurs above the segmental bronchus. It is commonly accompanied by bronchial stenosis or obstruction, which can easily lead to atelectasis. Accurately distinguishing lung cancer from atelectasis is important for tumor staging, delineating the radiotherapy target area, and evaluating treatment efficacy. This article reviews domestic and foreign literatures on how to define the boundary between central lung cancer and atelectasis based on multimodal images, aiming to summarize the experiences and propose the prospects.

Comparison of concurrent chemoradiotherapy with radiotherapy alone for locally advanced esophageal squamous cell cancer in elderly patients: A randomized, multicenter, phase II clinical trial.

This randomized, multicenter, phase II clinical trial was performed to compare the safety and efficacy of concurrent chemoradiotherapy using S-1 (CCRT) with radiotherapy alone (RT) for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). All eligible patients were randomly assigned to the CCRT group or the RT group at a 1:1 ratio. The CCRT group received 50.4 Gy radiotherapy concurrent with S-1 and the RT group received 59.4 Gy radiotherapy alone. The primary endpoints were toxicity and the overall response rate (ORR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). In total, 157 elderly patients with ESCC were recruited from December 2016 to March 2020. By June 2021, the median follow-up duration had reached 38 months. No grade 5 toxicities occurred in either group and the overall rate of severe toxicities (≥grade 3) was higher in the CCRT group (19.2% vs 7.6%; P = .037), particularly neutropenia (7.7% vs 1.3%; P = .06). The CCRT group presented a significantly higher ORR (83.3% vs 68.4%; P = .009) and prolonged PFS (25.7 vs 13.9 months; P = .026) than the RT group. The median OS was 27.3 months in the CCRT group and 19.1 months in the RT group (P = .59). For patients older than 70 years with locally advanced ESCC, concurrent chemoradiotherapy with S-1 had tolerable adverse effects and improved ORR and PFS compared to radiotherapy alone.

A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma.

BACKGROUND: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. METHODS: In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m2 intravenous paclitaxel on day 1, and 60-75 mg/m2 intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). CONCLUSIONS: The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

Azide-Locked Prodrug Co-Assembly into Nanoparticles with Indocyanine Green for Chemophotothermal Therapy.

Fabrication of self-delivery drug systems can surmount low drug bioavailability and achieve a precise therapeutic process. In this study, a hydrogen sulfide-responsive (H2S) small molecule prodrug was synthesized by linking two chemotherapy drugs, camptothecin (CPT) and gemcitabine (GT), using a reductive disulfide bond simultaneously with a lock GT strategy using a H2S-responsive azide group (denoted as N3-GT-CPT). The ingenious design endows the easy coprecipitation peculiarity of the prodrug with clinical indocyanine green (ICG) via a combined interaction force of hydrophobic, π-π stacking, and electrostatic interactions of anions and cations, thus producing a more stable and multifunctional therapeutic nanosystem. Considering the great photothermal and imaging ability of ICG, the obtained nanosystem showed an excellent therapeutic ability against colon tumors in vitro and in vivo with selective response to intercellular H2S, thus offering a good combination-based multiple therapy for treatment of tumors.

Nucleophilic Aromatic Substitution of 5-Bromo-1,2,3-triazines with Phenols.

Nucleophilic aromatic substitution (SNAr) reaction in classic textbook is a stepwise mechanism, and few examples of concerted reactions have been reported. Herein, we developed a concerted SNAr reaction of 5-bromo-1,2,3-triazines with phenols in which the nonclassic mechanism of this reaction could be revealed by calculation. Furthermore, the resulting 5-aryloxy-1,2,3-triazines could be used as convenient precursors to access biologically important 3-aryloxy-pyridines in one-pot manner.

D-aspartic acid protects against gingival fibroblasts inflammation by suppressing pyroptosis.

BACKGROUND: Peri-implantitis is the main cause of dental implant failure, which is associated with pyroptosis. The roles of D-aspartic acid (D-Asp) on pyroptosis and the mechanism of the protective effect of D-Asp on human gingival fibroblasts (HGFs) remain unknown. This study investigated the effects of D-Asp on the pyroptosis of HGFs induced by high mobility group box 1 protein (HMGB1). METHODS: The cytotoxic effects of D-Asp on HGFs was detected by Cell Counting Kit-8 assay, the membrane permeability was investigated by propidium iodide/ Hoechst 33,342 double staining, flow cytometry analysis, and lactate dehydrogenase releasing, The gene and protein expression levels were detected by real-time quantitative PCR, enzyme-linked immunosorbent assay, and Western blot, respectively. RESULTS: Cell viability analysis showed that D-Asp ≤ 30 mM had no cytotoxicity to HGFs. HMGB1 drastically raised the membrane permeability of HGFs, while 1/10/30 mM D-Asp suppressed the permeability and remained the integrity of the membrane. HMGB1 promoted the mRNA expression of NLRP3, caspase-1, GSDMD, IL-1ß, and IL-18, and the protein expression of IL-1ß, IL-18, caspase-1, GSDMD, and NLRP3. CONCLUSIONS: With the pretreatment of HGFs with D-Asp of 1/10/30 mM for 24 h, the cell membrane permeability was reduced and the expression of NLRP3, caspase-1, GSDMD, IL-1ß, and IL-18 was significantly decreased compared with the HMGB1 group, indicating the competitive antagonism of D-Asp against HMGB1 on the binding with toll-like receptors. Hence, this study may provide a novel insight into preventing pyroptosis and propose a new strategy for the treatment of peri-implantitis.

SLC7A11 regulated by NRF2 modulates esophageal squamous cell carcinoma radiosensitivity by inhibiting ferroptosis.

BACKGROUND: Solute carrier family 7 member 11(SLC7A11) is a component of cysteine/glutamate transporter, which plays a key role in tumor growth; however, its underlying effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to clarify SLC7A11's expression and correlation with nuclear expression of nuclear factor erythroid-2 (NRF2)-associated radioresistance in ESCC. METHODS: We included 127 ESCC patients who received radical chemoradiotherapy. Immunohistochemical staining was used to detect SLC7A11 and NRF2 nuclear expression, and the relationship between clinicopathological characteristics and survival rates or therapy response were evaluated. Western blot, dual-reporter assays and Chromatin immunoprecipitation (ChIP)-sequencing were used to analyze their relationship in vitro. Their roles in radioresistance were then investigated through multiple validation steps. RESULTS: NRF2 nuclear expression and SLC7A11 expression were overexpressed in ESCC tissues and were positively correlated with one another. NRF2 nuclear expression was significantly associated with tumor length, lymph node metastasis, and TNM stage, while SLC7A11 expression was associated with lymph node metastasis. Patients with high NRF2 nuclear expression and SLC7A11 expression had significantly shorter overall and progression-free survival, and poor treatment response. The multivariate model showed that NRF2 nuclear expression and SLC7A11 expression, sex and tumor location are independent prognostic factors. In vitro analysis confirmed that hyperactivation of NRF2 induced SLC7A11 expression by directly binding to its promoter region, promoting radioresistance, reducing radiotherapy-induced lipid peroxidation levels, PTGS2 expression, and radiotherapy-related ferroptosis morphologic features. CONCLUSION: Our study reveals a connection between high SLC7A11 expression and NRF2 nuclear expression in patients with ESCC that was related to worse survival and poorer therapy outcomes. SLC7A11-mediated ferroptosis inhibition induced NRF2-associated radioresistance, highlighting potential of NRF2/SLC7A11/ferroptosis axis as future therapeutic targets against therapy resistance biomarker.

Inter-observer variations of the tumor bed delineation for patients after breast conserving surgery in preoperative magnetic resonance and computed tomography scan fusion.

PURPOSE: Tumor bed (TB) delineation based on preoperative magnetic resonance imaging (pre-MRI) fused with postoperative computed tomography (post-CT) were compared to post-CT only to define pre-MRI may aid in improving the accuracy of delineation. METHODS AND MATERIALS: The pre-MRI imaging of 10 patients underwent radiotherapy (RT) after breast conserving surgery (BCS) were reviewed. Post-CT scans were acquired in the same prone position as pre-MRI. Pre-MRI and post-CT automatically match and then manual alignment was given to enhance fusion consistency. Three radiation oncologists and 2 radiologists delineated the clinical target volume (CTV) for CT-based. The gross target volume (GTV) of pre-MRI-based was determined by the volume of tumor acquired with 6 sequences: T1, T2, T2W-SPAIR, DWI, dyn-eTHRIVE and sdyn-eTHRIVE, expended 10 mm to form the CTV-pre-MRI. Planning target volume (PTV) for each sequence was determined by CTV extended 15 mm, trimmed to 3 mm from skin and the breast-chest wall interface. The variability of the TB delineation were developed as follows: the mean volume, conformity index (CI) and dice coefficient (DC). RESULTS: The mean volumes of CTV and PTV delineated with CT were all larger than those with pre-MRI. The lower inter-observer variability was observed from PTV, especially in sdyn-eTHRIVE in all sequences. For each sequence of pre-MRI, all DCs were larger than post-CT, and the largest DC was observed by sdyn-eTHRIVE sequence fusion to post-CT. The overlap for PTV was significantly improved in the pre-MRI-based compared with the CT-based. CONCLUSIONS: TB volumes based on pre-MRI were smaller than post-CT with CVS increased. Pre-MRI provided a more precise definition of the TB with observers performed a smaller inter-observer variability than CT. Pre-MRI, especially in sdyn-eTHRIVE sequence, should help in reducing treatment volumes with the improved accuracy of TB delineation of adjuvant RT of breast cancer.

Investigation on the influence of additives on the oriented dissolution of calcite.

Similar to the crystal growth process, additives have a strong influence on the dissolution process of crystals. Studies on the dissolution process may shed light on understanding the biomineralization and bioinspired crystallization process. The influence of different kinds of additives including surfactants and polymers on the dissolution process of calcite {104} planes was investigated in detail in this work. The additives can be classified into three kinds according to their influence on the dissolution process of calcite under different concentration windows. The additives show three different kinds of dissolution behaviors with the increase of additive concentrations according to the tomographic variation of the calcite surface after the dissolution process. There are four dissolution modes of calcite while changing the additive concentrations in the solution. Rhombohedral etch pits with [4[combining macron]41] and [481[combining macron]] step edges are formed on the calcite {104} planes after the dissolution process at low additive concentrations (mode I). Calcite micropyramids begin to appear on the calcite surface and the densities of micropyramids increase with the increase of the additive concentrations until they cover the entire calcite surface after the dissolution process at medium additive concentrations (mode II). Instead of micropyramids, large pyramids with [481[combining macron]] and [4[combining macron]41] step edges and a size of about 50 µm form after the dissolution process at high additive concentrations (modes III and IV). We propose that the different anisotropic dissolution behaviors of calcite are strongly related to the concentrations and the adsorption features of the additives on the calcite surface. The additives may act as inhibitors of calcite dissolution, possibly through adsorption on calcite surfaces without preferred adsorption, or adsorption at specific kink sites or step edges. The influence of additives on the oriented dissolution of calcite is generally related to the adsorption density and homogeneity of additives on the calcite substrates.

Local therapy for oligometastatic esophageal squamous cell carcinoma: a prospective, randomized, Phase II clinical trial.

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).

Lay abstract The ESO-Shanghai 13 trial is a prospective, multicenter, randomized, Phase II trial to assess the impact of combined local treatment (such as radiotherapy, surgery and thermal ablation) and chemical drugs for patients with esophageal squamous cell carcinoma. Patients with four or less metastases and controlled esophageal lesion will be enrolled. The authors will recruit a total of 102 patients over 3 years from approximately five centers. All patients will be randomized and receive either chemical drugs alone or chemical drugs plus local treatment with the same probability. Patients will then be observed after treatment until disease progression or death or the end of the trial. Patients will need to report their symptoms and physical status and fill out quality of life scales during the treatment and follow-up period.

Synergistic effects of D-arginine, D-methionine and D-histidine against Porphyromonas gingivalis biofilms.

Porphyromonas gingivalis biofilms are implicated in the pathology of peri-implantitis and periodontitis. In this study, D-arginine (R), D-methionine (M), D-histidine (H), and a mixture of these D-amino acids (D-AAs) were investigated as an effective therapeutic strategy against P. gingivalis biofilms. The bacterial growth activity and minimum inhibitory concentrations were determined for each D-AA, along with the effects of the D-AAs mixture on biofilm development, morphology, structure, extracellular polysaccharides (EPS), cytotoxicity towards commensals, and bacterial structure. The D-AA mixture delayed the proliferation of P. gingivalis, changed its membrane structure, and decreased biofilm thickness and integrity, as compared with individual D-AAs. The EPS content increased with the concentration of D-AAs. The present study shows that a 4 mM RMH, triple D-AA mixture, enhanced deleterious effects on P. gingivalis biofilms without any cytotoxicity compared with individual D-AAs, thus providing a new strategy for the treatment of peri-implantitis and periodontitis.

Correction to: Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis.

An amendment to this paper has been published and can be accessed via the original article.

Prodrug-Based Versatile Nanomedicine for Enhancing Cancer Immunotherapy by Increasing Immunogenic Cell Death.

Nanoparticle-based tumor immunotherapy has emerged to show great potential for simultaneously regulating the immunosuppressive tumor microenvironment, reducing the unpleasant side effects, and activating tumor immunity. Herein, an excipient-free glutathione/pH dual-responsive prodrug nanoplatform is reported for immunotherapy, simply by sequentially liberating 5-aminolevulinic acid and immunogenically inducing doxorubicin drug molecules, which can leverage the acidity and reverse tumor microenvironment. The obtained nanoplatform effectively boosts the immune system by promoting dendritic cell maturation and reducing the number of immune suppressive immune cells, which shows the enhanced adjunctive effect of anti-programmed cell death protein 1 therapy. Overall, the prodrug-based immunotherapy nanoplatform may offer a reliable strategy for improving synergistic antitumor efficacy.

Patterns of regional lymph node failure of locally advanced hypopharyngeal squamous cell carcinoma after first-line treatment with surgery and/or intensity-modulated radiotherapy.

BACKGROUND: To identify the spatial patterns of regional lymph node failure of locally advanced hypopharyngeal squamous cell carcinoma (SCC) after first-line treatment with surgery and/or intensity-modulated radiotherapy (IMRT). METHODS: We retrospectively obtained the clinicopathological characters of 123 hypopharyngeal SCC patients, and investigated the patterns of regional lymph node failure. Univariate and multivariate logistic regression were used to determine the risk factors of regional lymph node failure. RESULTS: Forty patients (32.5% of total patients) were suffered regional lymph node failure. In these patients, the ipsilateral neck level II nodal failure account for 55.0% (22/40) followed by level III 30.0% (12/40), level VIb 15.0% (6/40), level VII 15.0% (6/40), and level IV 5.0% (2/40). In addition, 17.5% (7/40) patients suffered contralateral neck level II nodal failure and 7.5% (3/40) patients suffered level III nodal failure. The common failure levels were the II (7/46, 15.2%), III (4/46, 8.7%), VIb (4/46, 8.7%), and VII (5/46, 10.9%) for treatment by surgery. The lymph node recurrence and persistent disease at levels II (19/77, 24.7%) and III (10/77, 13.0%) remained the major cause of failure following curative intent of IMRT. The postoperative radiation significantly decreased the risk of regional lymph node failure (OR = 0.082, 95% CI: 0.007-1.000, P = 0.049); and the radiologic extranodal extension significantly increased the risk of regional lymph node failure (OR = 11.07, 95% CI: 2.870-42.69, P < 0.001). CONCLUSIONS: Whatever the treatment modality, the lymph node failure at level II and III was the most popular pattern for hypopharyngeal SCC. Moreover, for patients who underwent surgery, the nodal failure at level VIb and VII was frequent. Thus, postoperative radiation of level VIb and VII may give rise to benefit to locally advanced hypopharyngeal SCC patients.