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To evaluate the therapeutic efficacy of cyclin-dependent kinase (CDK) inhibition in combination with ionizing radiation for lung cancer.Human lung adenocarcinoma (A549) and squamous cell carcinoma (H520) cells were used to evaluate the therapeutic efficacy of CDK inhibition in combination with ionizing radiation in vitro using colony formation assay, γH2AX immunofluorescence staining, western blotting, and cell cycle phase analysis. We also performed in vivo evaluations of ectopic tumor growth.In vitro pretreatment with the CDK inhibitor, seliciclib, before irradiation significantly decreased the survival of A549 and H520 cells in a dose-dependent manner. Although CDK inhibition alone did not increase the intensity of γH2AX foci, its combination with ionizing radiation increased DNA double-strand breaks, as shown by γH2AX immunofluorescence staining and western blotting. The combination of CDK inhibition and ionizing radiation-induced G2/M arrest and increased apoptosis, as evidenced by the increased proportion of cells in G2/M arrest, subG1 apoptotic population, and expression of apoptotic markers (cleaved PARP-1 and cleaved caspase-3). Mechanistic studies showed reduced expression of cyclin A with combined treatment, indicating cell cycle shifting effects. An in vivo xenograft model showed that the combination of CDK inhibition and ionizing radiation delayed xenograft tumor growth, and increased the proportion of cleaved PARP-1- and cleaved caspase-3-positive cells, compared to either treatment alone.We provide preclinical tumoricidal evidence that the combination of CDK inhibition and ionizing radiation is an efficacious treatment for lung cancer.

Epithelial cysts run a high risk of recurrence and conversion to sheet-like ingrowth after surgical intervention. In this retrospective study, we introduced a modified iridectomy for treatment of secondary epithelial iris cysts (EICs) in the anterior chamber. Twenty-nine patients (29 eyes) aged 2–61 years received “open iridectomy” for EICs between April 1995 and July 2019. After viscodissection, most of the cyst wall was cut using a 20-gauge aspiration cutter via a 2.5-mm clear corneal incision. The residue closely adhering to the iris stroma was remained to avoid photophobia and diplopia. At 3 months, best corrected visual acuity was ≥ 20/100 in 55.5% (15/27, except two pediatric patients with poor cooperation) of patients. Among the eight patients suffering partial corneal edema preoperatively, six patients received surgery treatment at 3–6.5 months, and the cornea in the other two patients became transparent after medication. In a mean follow-up of 47.4 months, recurrence occurred in 3 patients at 7, 37, and 118 months, respectively. The percentage of treatment success was 96%, 87%, and 65% at 1, 5, and 10 years, respectively. “Open iridectomy” was effective for EICs, with a minimal invasion, less damage to the corneal endothelium, and a low recurrence rate.

Treatment of stage IV esophageal cancer is traditionally palliative, but treatment response is usually poor. The role of surgery in the treatment of advanced esophageal cancer remains controversial. We sought to determine whether surgical treatment followed by neoadjuvant chemoradiation therapy might provide survival benefits for these patients. A retrospective review of 163 esophageal cancer patients with M1 disease (distant organ metastasis) treated at a tertiary medical center hospital was performed from April 2002 to June 2021. Patient demographics and cancer staging, treatment, and disease recurrence, and time of follow up were included for analysis. Univariate and multivariate analysis was performed for overall survival and progression-free survival analysis. Propensity score matching based on patient age and tumor staging characteristics was also performed for analysis. 124 patients were treated by CCRT alone and 39 treated by CCRT plus surgery. 3-year and 5-year progression free survival was 17.7% and 8.9% for CCRT+surgery group vs 0.8% and 0.0% in CCRT only group. (p = 0.019) 3- and 5-year survival was 24.0% and 12.0% in CCRT plus surgery group compared to 2.8% and 1.4% for CCRT only group (p = 0.009). Propensity matching of 39 CCRT plus surgery patients and 78 CCRT-only patients showed similar results (17.5% & 8.5% PFS vs 1.3% & 0.0% for PFS, 24.0% and 12.0% vs 3.9% and 1.9% OS). Surgical resection following CCRT treatment may improve progression-free survival and overall survival for selected patients of esophageal cancer with M1 disease. Surgical indication should be judicious, and further follow up studies should be performed.

Background: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan. Methods: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment. Results: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P

This phase 2 trial aimed to determine whether xenon-enhanced ventilation computed tomography (XeCT)-guided functional-lung-avoidance radiation therapy could reduce the radiation pneumonitis (RP) rate in patients with lung cancer undergoing definitive chemoradiation therapy.Functional lung ventilation was measured via pulmonary function testing (PFT) and XeCT. A standard plan (SP) without reference to XeCT and a functional-lung-avoidance plan (fAP) optimized for lowering the radiation dose to the functional lung at the guidance of XeCT were designed. Dosimetric parameters and predicted RP risks modeled by biological evaluation were compared between the 2 plans in a treatment planning system (TPS). All patients received the approved fAP. The primary endpoint was the rate of grade ≥2 RP, and the secondary endpoints were the survival outcomes. The study hypothesis was that fAP could reduce the rate of grade ≥2 RP to 12% compared with a 30% historical rate.Thirty-six patients were evaluated. Xenon-enhanced total functional lung volumes positively correlated with PFT ventilation parameters (forced vital capacity, P = .012; forced expiratory volume in 1 second, P = .035), whereas they were not correlated with the diffusion capacity parameter. We observed a 17% rate of grade ≥2 RP (6 of 36 patients), which was significantly different (P = .040) compared with the historical control. Compared with the SP, the fAP significantly spared the total ventilated lung, leading to a reduction in predicted grade ≥2 RP (P = .001) by TPS biological evaluation. The median follow-up was 15.2 months. The 1-year local control (LC), disseminated failure-free survival (DFFS), and overall survival (OS) rates were 88%, 66%, and 91%, respectively. The median LC and OS were not reached, and the median DFFS was 24.0 months (95% confidence interval, 15.7-32.3 months).This report of XeCT-guided functional-lung-avoidance radiation therapy provided evidence showing its feasibility in clinical practice. Its benefit should be assessed in a broader multicenter trial setting.

A postcataract surgery complication in patients with retinitis pigmentosa (RP) is lens capsular contraction. To identify potential proteins contributing to this phenomenon, high-performance liquid chromatography/mass spectrometry-based proteomic analysis was conducted with aqueous humor samples collected from 11 patients who underwent cataract surgeries, with four patients diagnosed as RP and cataract (RP group) and the other seven with only senile cataract group. The upregulated proteins in the RP group were enriched in wound response, while downregulated proteins were enriched in cell adhesion and lens crystallins. Receptors of two dramatically upregulated proteins tenascin-C (TNC) and serotransferrin were found expressed in human lens epithelial cells (HLEs). TNC can promote primary HLEs proliferation and cell line HLE-B3 migration. This study indicates aqueous humor proteomic analysis serves as an effective way to unveil the pathogenesis of RP complications. TNC is a potential target of stimulating HLEs proliferation in RP concomitant cataract patients that worth further research.

BACKGROUND Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy. OBJECTIVE To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy. METHODS HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions). RESULTS The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p

BACKGROUND We hypothesized that patients with head and neck squamous cell carcinoma (HNSCC) with smoking cessation during curative chemoradiotherapy (CRT) had fewer complications and lower tumor progression risks. METHODS Sixty-three patients with nonmetastatic HNSCC who were smokers at diagnosis (carbon monoxide [CO] breath concentrations ≥3 ppm) and underwent curative CRT were prospectively enrolled. Successful smoking cessation throughout CRT was confirmed by CO breath concentrations

We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance–positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT). Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8–32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans 277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031). The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. Methods This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. Results Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p Ktrans, and kep, showed strong linear correlations (p p = 0.004), MTV values (p kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10− 3/min (p = 0.069), and kep > 900 10− 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. Conclusions The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI), low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS), patients with age &gt, 60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

This study investigated ultrashort echo time (UTE) sequences in 1.5 T magnetic resonance imaging (MRI) for small lung nodule detection.A total of 120 patients with 165 small lung nodules before video-associated thoracoscopic resection were enrolled. MRI sequences included conventional volumetric interpolated breath-hold examination (VIBE, scan time 16 s), spiral UTE (TE 0.05 ms) with free-breathing (scan time 3.5-5 min), and breath-hold sequences (scan time 20 s). Chest CT provided a standard reference for nodule size and morphology. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis.The nodule detection rate was significantly higher in spiral UTE free-breathing ( 78%, p 0.05) and breath-hold sequences ( 75%, p 0.05) compared with conventional VIBE ( 55%), reaching 100% when nodule size was 16 mm, and reaching 95% when nodules were in solid morphology, regardless of size. The inter-sequence reliability between free-breathing and breath-hold spiral UTE was good (κ 0.80). Inter-reader agreement was also high (κ 0.77) for spiral UTE sequences. Nodule size measurements were consistent between CT and spiral UTE MRI, with a minimal bias up to 0.2 mm.Spiral UTE sequences detect small lung nodules that warrant surgery, offers realistic scan times for clinical work, and could be implemented as part of routine lung MRI.

Background Cardiovascular magnetic resonance (CMR)–derived extracellular volume (ECV) requires a hematocrit (Hct) to correct contrast volume distributions in blood. However, the timely assessment of Hct can be challenging and has limited the routine clinical application of ECV. The goal of the present study was to evaluate whether ECV measurements lead to significant error if a venous Hct was unavailable on the day of CMR. Methods 109 patients with CMR T1 mapping and two venous Hcts (Hct0: a Hct from the day of CMR, and Hct1: a Hct from a different day) were retrospectively identified. A synthetic Hct (Hctsyn) derived from native blood T1 was also assessed. The study used two different ECV methods, (1) a conventional method in which ECV was estimated from native and postcontrast T1 maps using a region-based method, and (2) an inline method in which ECV was directly measured from inline ECV mapping. ECVs measured with Hct0, Hct1, and Hctsyn were compared for each method, and the reference ECV (ECV0) was defined using the Hct0. The error between synthetic (ECVsyn) and ECV0was analyzed for the two ECV methods. Results ECV measured using Hct1 and Hctsyn were significantly correlated with ECV0 for each method. No significant differences were observed between ECV0 and ECV measured with Hct1 (ECV1; 28.4 ± 6.6% vs. 28.3 ± 6.1%, p = 0.789) and between ECV0 and ECV calculated with Hctsyn (ECVsyn; 28.4 ± 6.6% vs. 28.2 ± 6.2%, p = 0.45) using the conventional method. Similarly, ECV0 was not significantly different from ECV1 (28.5 ± 6.7% vs. 28.5 ± 6.2, p = 0.801) and ECVsyn (28.5 ± 6.7% vs. 28.4 ± 6.0, p = 0.974) using inline method. ECVsyn values revealed relatively large discrepancies in patients with lower Hcts compared with those with higher Hcts. Conclusions Venous Hcts measured on a different day from that of the CMR examination can still be used to measure ECV. ECVsyn can provide an alternative method to quantify ECV without needing a blood sample, but significant ECV errors occur in patients with severe anemia.

Background The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. Methods We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. Results One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. Conclusions Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. Trial registration ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

Bacteria associated with postoperative endophthalmitis mostly originate from the normal bacterial flora of the patient’s conjunctiva and eyelids, so the incidence of endophthalmitis may be reduced by eliminating the ocular and adnexal flora before surgery. We assessed the effectiveness of eyedrops of 0.5% levofloxacin and 5.0% povidone-iodine (PVI) in reducing conjunctival bacterial flora by metagenomic analysis. A total of 2.4 × 106 high-quality sequencing reads were generated from 93 conjunctival samples obtained from 31 eyes scheduled for cataract surgery before prophylactic therapy (group 1), after administration of 0.5% levofloxacin eyedrops into the conjunctival sac 8 times before surgery (group 2), and at 3 minutes after instillation of 5.0% PVI solution in the conjunctival sac (group 3) followed by surgery irrigation. The alpha diversity and beta diversity results demonstrated that group 3 had the least richness and biodiversity. Corynebacterium, Pseudomonas, Staphylococcus, Acinetobacter, and Streptococcus were predominant in all samples. The relative abundance of these bacterial species was 30.94%, 27.48%, 5.26%, 4.55%, and 2.61% in group 1, 16.32%, 44.10%, 2.19%, 5.39%, and 0.97% in group 2, and 5.90%, 65.55%, 0.39%, 5.36%, and 0.10% in group 3, respectively. The most easily and difficultly eliminated were Corynebacterium and Pseudomonas, respectively. In conclusion, the metagenomic analysis using high-throughput sequencing provides a scientific way for evaluating the effectiveness of a disinfection method from the perspective of analyzing the composition and diversity of the conjunctival microbiome. Despite the use of preoperative antisepsis regimens, the ocular surface of patients receiving cataract surgery could not be rendered completely aseptic, indicating that more strict disinfection methods need to be adopted to reduce the risk for anterior chamber contamination and endophthalmitis after cataract surgery.

Lymph node metastasis (LNM) identification is the most clinically important tasks related to survival and recurrence from lung cancer. However, the preoperative prediction of nodal metastasis remains a challenge to determine surgical plans and pretreatment decisions in patients with cancers. We proposed a novel deep prediction method with a size-related damper block for nodal metastasis (Nmet) identification from the primary tumor in lung cancer generated by gemstone spectral imaging (GSI) dual-energy computer tomography (CT). The best model is the proposed method trained by the 40 keV dataset achieves an accuracy of 86 % and a Kappa value of 72 % for Nmet prediction. In the experiment, we have 11 different monochromatic images from 40∼140 keV (the interval is 10 keV) for each patient. When we used the model of 40 keV dataset, there has significant difference in other energy levels (unit of keV). Therefore, we apply in 5-fold cross-validation to explain the lower keV is more efficient to predict Nmet of the primary tumor. The result shows that tumor heterogeneity and size contributed to the proposed model to estimate whether absence or presence of nodal metastasis from the primary tumor.

Purpose To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). Materials and Methods We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans, kep, ve, vp, and iAUC60. Chest computed tomography (CT) was performed at 3 months after SBRT. Results SBRT treatment led to tumor changes including significant decreases in the SUVmax (–61%, P 10 (P = 0.083). Conclusion In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

C57BL/6 mice implanted in the flank with murine Lewis lung carcinoma cells were randomized into control, anti-angiogenic, anti-PD-L1, radiotherapy (RT), RT + anti-angiogenic, RT + anti-PD-L1, and RT + anti-PD-L1 + anti-angiogenic therapy groups. Immune response and immunophenotyping were determined by flow cytometry. Vasculature analysis after RT and anti-angiogenic therapy was assessed by quantified power Doppler sonography. Antitumor response, survival, and rechallenged tumor growth were evaluated. RT increased PD-L1 expression on CD8+ T, CD4+ T, dendritic, myeloid-derived suppressor cells (MDSCs), and tumor cells and increased PD-1 expression on CD8+ and CD4+ T cells. Anti-angiogenic therapy insignificantly decreased the RT-induced PD-1 expression on CD8+ and CD4+ T cells, implying a weak reversal of the immune-suppressive environment. Transient vessel collapse was observed within days after RT, and blood flow recovered at 1 week after RT. RT + anti-PD-L1 suppressed the tumor growth, improved survival, and prolonged immune memory capable of protecting against tumor recurrence, evidenced by local accumulation of CD8+ T cells and reduction in MDSCs in microenvironment. Similar and more prominent effects were observed when anti-VEGF was added to RT + anti-PDL1 therapies, implying an additive, rather than synergistic, antitumor immunity. Phenotypic analyses revealed that anti-cancer treatments increased the proportion of effector memory T cells in TILs and splenocytes, and RT, alone or in combination with other treatments, further increased the proportion of central memory T cells in splenocytes. These results provide evidence on operating the immunosuppressive tumor environment and offer insights into the design of the new combination treatment.

Aim To investigate the ocular surface microbiome profile of patients with fungal keratitis (FK) through bacterial 16S rDNA sequencing. Methods The swab samples were collected from 8 patients with FK (Group 1 from the corneal ulcer, Group 2 from the conjunctival sac of the infected eyes, and Group 3 from the conjunctival sac of the fellow eyes) and 10 healthy eyes (Group 4 from the conjunctival sac). Bacterial 16S rDNA V4-V5 region sequencing was performed to characterize the bacterial communities on the ocular surfaces of the patients with FK. Results Our metagenomic data showed that 97% of the sequence reads were categorized into 245 distinct bacterial genera, with 67.75±7.79 genera detected in Group 1, 73.80±13.44 in Group 2, 74.57±14.14 in Group 3, and 89.60±27.49 in Group 4. Compared with the healthy eyes (Group 4), both infected (Groups 1 and 2) and fellow eyes (Group 3) of the patients with FK showed reduced bacterial diversity and altered ocular surface microbiota compositions, with lower abundance of Corynebacterium and Staphylococcus and higher abundances of Pseudomonas, Achromobacter, Caulobacter and Psychrobacter. Conclusion Our report depicts the altered ocular surface bacterial community structures both in the affected and fellow eyes of patients with FK. These changes may contribute to the pathogenesis of FK or the increased risk for FK.

This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib. Human esophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models. Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone. The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone.

We evaluated the prognostic significance of immunologic inhibitory biomarkers in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma levels of soluble MHC class I polypeptide-related sequence A (sMICA) and transforming growth factor-β1 (TGF-β1) were measured before and 2 weeks after CRT. The median follow-up was 32.9 months (range: 12.4-40.6 months). The pre-treatment sMICA (p < 0.001) and TGF-β1 (p < 0.001) levels were significantly increased in HNSCC patients, compared to healthy controls. In HNSCC patients, the median pre-CRT and post-CRT sMICA levels were 43.1 pg/mL and 65.3 pg/mL, respectively, while the median pre-CRT and post-CRT TGF-β1 levels were 57.7 ng/mL and 36.0 ng/mL, respectively. After CRT, 19 patients (63.3%) exhibited persistently elevated sMICA, six patients (20.0%) exhibited persistently elevated TGF-β1, and five patients (16.7%) exhibited persistently elevated sMICA and TGF-β1. Patients with persistently elevated sMICA and TGF-β1 after CRT experienced an earlier tumor progression (p = 0.030), and poor overall survival (p = 0.010). Our results suggest that HNSCC patients who exhibit persistently elevated sMICA and TGF-β1 levels after CRT are at higher risk of tumor progression or death.

To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC).We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, KSBRT treatment led to tumor changes including significant decreases in the SUVIn patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome.2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199.

AIM To compare the visual functional outcomes with accommodating and multifocal intraocular lenses (IOLs). METHODS Our retrospective comparative study included 51 patients (60 eyes) received implantation of an accommodating IOL (Tetraflex; 16 patients, 20 eyes), a refractive multifocal IOL (ReZoom; 18 patients, 20 eyes), or a diffractive multifocal IOL (ZMA00; 17 patients, 20 eyes). Subjective refraction, visual acuity, contrast sensitivity (CS), intraocular aberration, and subjective photic phenomena were detected at 3mo after surgery. RESULTS The spherical equivalent in the three groups was -0.38±0.54 D, 0.14±0.56 D, and 0.35±0.41 D, respectively. No statistically significant differences were found in uncorrected and corrected distance visual acuity and uncorrected intermediate visual acuity among the groups (P=0.39). The ReZoom group had significantly better distance-corrected intermediate visual acuity than the ZMA00 group (P=0.003). The ZMA00 group had significantly better near visual acuity than the other groups (P

To assess the safety, efficacy, clinical outcomes, and prognostic factors associated with transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) for nonvariceal upper gastrointestinal (GI) hemorrhage in hemodynamically unstable patients.Between January 2008 and December 2012, 49 hemodynamically unstable patients (systolic blood pressure90 mm Hg and ongoing transfusion requirement) underwent emergency TAE with NBCA for nonvariceal upper GI bleeding and were included in the study. The technical (cessation of extravasation) and clinical (no residual bleeding within 7 d) success rates, incidence of ischemic complications, and clinical and technical predictors of recurrent bleeding within 30 days were analyzed.The technical and clinical success rates were 98% and 71%, respectively. There were no ischemic bowel complications; one patient experienced hepatic infarction with elevated liver enzymes. The incidence of major complications was 2%. The incidence of rebleeding within 30 days was 39%. Hematologic malignancies (P = .017), coagulopathy (P = .003), steroid pulse therapy (P = .025), and the absence of NBCA in the target lesions (P = .003) were associated with recurrent bleeding.NBCA embolization can be safely performed in hemodynamically unstable patients with active nonvariceal upper GI bleeding. The clinical factors associated with rebleeding might influence the clinical outcome.

Objective: This study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT). Materials and Methods: Lung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators. Results: Significant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R 2 = 0.340, p = 0.023), RV stroke volume (R 2 = 0.406, p = 0.011), and RV cardiac output (R 2 = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed. Conclusion: The study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients. Index terms: Pulmonary hypertension; Chronic obstructive pulmonary disease; Emphysema; Right ventricular function

Since December 2009, after breast-conserving surgery for Stage 0–I cancer of the left breast, 21 women with relatively pendulous breasts underwent computed tomography prone and supine simulations. The adjuvant radiotherapy was 50 Gy in 25 fractions to the left breast alone. Four plans—conventional wedged tangents and forward intensity-modulated radiotherapy (fIMRT) in supine and prone positions—were generated. fIMRT generated better homogeneity in both positions. Prone position centralized the breast tissue by gravity and also shortened the breast width which led to better conformity in both planning techniques. Prone fIMRT significantly reduced doses to left lung, Level I and Level II axilla. The mean cardiac doses did not differ between positions. Among the four plans, prone fIMRT produced the best target dosimetry and normal organ sparing. In subgroup analysis, patients with absolute breast depth > 7 cm in the prone position or breast depth difference > 3 cm between positions had significant cardiac sparing with prone fIMRT. Sixteen patients with significant cardiac sparing in prone position were treated using prone fIMRT and the others using supine fIMRT. All patients received a supine electron tumor bed boost of 10 Gy in 5 fractions. No patients developed Grade 2 or worse acute or late toxicities. There was no difference in the number of segments or beams, monitor units, treatment time, or positioning reproducibility between prone and supine positions. At a median follow-up time of 26.8 months, no locoregional or distant recurrence or death was noted.

Background: Microwave ablation (MWA) of lung tumors is a new approach for local tumor control. The purpose of this retrospective study was to evaluate the preliminary results of safety and efficacy of MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) for local tumor control of thoracic malignancies. Methods: From December 1, 2013 to February 1, 2016, there were total 32 lung tumors among 15 patients (7 men, 8 women, age range 43–82 years, mean 57.8±11.1 years of age) receiving MWA of thoracic neoplasms, including lung adenocarcinoma (n=5), metastatic colorectal cancer (n=7), invasive thymoma (n=1), metastatic uterine leiomyosarcoma (n=1), and metastatic ampullary carcinoma (n=1). Mean tumor size was 13.5 mm (range, 3.0–32.0 mm). The mean sequential ablation during each MWA was 2.3±1.1 times (range, 1–5 times). The outcomes of ablation were evaluated by follow-up computed tomography (CT) scans and the complications were assessed by medical records and CT scan after ablation. Results: The mean follow-up interval of each tumor was 446.8 days (range, 196–902 days). Local tumor recurrence was found in 5 of the 32 tumors resulting in a local control rate 84.4%. No MWA-related mortality was noted. After MWA, the incidence of pneumothorax was 37.5% (12/32). Only one patient with pneumothorax required air evacuation. Third-degree skin burn adjacent to the entry site occurred in one patient and required debridement and closure with flap. Conclusions: After appropriate patient selection, MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) is an effective and safe procedure for local tumor control of recurrent and metastatic lung tumors.

// Jenny Ling-Yu Chen 1,2 , Yu-Sen Huang 3,4 , Sung-Hsin Kuo 1,5 , Ruey-Long Hong 1 , Jenq-Yuh Ko 6 , Pei-Jen Lou 6 and Chun-Wei Wang 1 1 Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Radiation Oncology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan 3 Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 4 Department of Medical Imaging, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan 5 Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan 6 Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Correspondence to: Chun-Wei Wang, email: // Keywords : intensity-modulated radiation therapy; conformal radiation therapy; nasopharyngeal carcinoma; survival outcomes; late toxicities Received : May 23, 2016 Accepted : October 12, 2016 Published : October 18, 2016 Abstract Purpose: To examine the survival outcomes and late toxicity profiles of three-dimensional conformal radiation therapy (3DCRT) vs . intensity-modulated radiation therapy (IMRT) for patients with nasopharyngeal carcinoma (NPC). Methods: Three hundred and seventy-four patients with newly diagnosed, non-metastatic, NPC who were curatively treated with 3DCRT between 2004 and 2006 and 481 patients treated with IMRT between 2007 and 2009 were analyzed. Patients were categorized as having advanced-stage disease (stage III, IVA, and IVB disease; n = 709) or early-stage disease (stage I and II; n = 146). The median follow-up time was 90.3 months for patients treated with 3DCRT and 86.3 months for patients treated with IMRT. Results: For early-stage patients, the outcomes of IMRT vs . 3DCRT were similar considering locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). For advanced-stage patients, IMRT was associated with better LRC compared with 3DCRT (5-year LRC rate: 85.6% vs . 76.6%, respectively; p = 0.035) and OS (5-year OS rate: 82.3% vs . 71.8%, respectively; p = 0.002), whereas DMFS was similar for both treatments (5-year DMFS rate: 80.9% vs . 79.0%, respectively; p = 0.324). Furthermore, the IMRT technique was more beneficial for patients with T4 disease. Late toxicities occurred more frequently in patients treated with 3DCRT than in those treated with IMRT (grade ≥3 neck fibrosis: 6.7% vs . 3.7%, respectively, p = 0.036; radiographic temporal lobe necrosis: 10.2% vs . 4.4%, respectively, p < 0.001). Conclusions: Compared with 3DCRT, IMRT offered better LRC in patients with advanced-stage non-metastatic NPC, which corresponded with better OS.

A 46-year-old man with a history of alcohol abuse was admitted to the emergency department with drowsiness, septic shock and chronic back pain that had exacerbated quickly over the past 2 days. His medical history was limited to alcoholic liver cirrhosis without regular medical attention. Physical and laboratory examinations revealed leukocytosis, thrombocytopenia, coagulopathy and deteriorated …

To evaluate the clinical, pathologic, and imaging findings of solid pseudopapillary neoplasm (SPN) of the pancreas in order to differentiate benign from malignant pancreatic neoplasms.We retrospectively identified 23 patients with 24 SPNs confirmed by pathology at National Taiwan University Hospital between January, 2001 and March, 2012. All computed tomography and magnetic resonance imaging were reviewed by two radiologists in consensus. Each tumor was analyzed for location of tumor, tumor margin, proportion of solid component, capsule morphology, growth pattern, presence of calcification, presence of upstream pancreatic duct dilatation, and enhancement pattern.SPN of the pancreas demonstrated variable degrees of hemorrhagic degeneration and calcification. Focal discontinuity of capsule was consistently observed in five malignant tumors (p = 0.004). There were no statistical differences between benign and malignant tumors based on location of tumor, tumor margin, proportion of solid component, growth pattern, presence of calcification, presence of upstream pancreatic duct dilatation, or enhancement patternAmong the various imaging features, we found that focal discontinuity of the capsule may suggest malignancy.