Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

Comparative Analysis of Oncologic Outcomes in Patients with Squamous Cell Carcinoma of the Uterine Cervix with High-Risk Features for Para-Aortic Recurrence: Prophylactic Extended-Field versus Pelvic Chemoradiotherapy.

Purpose: To compare the oncologic outcomes of prophylactic extended-field radiation therapy (EFRT) and whole pelvic radiation therapy (WPRT) in cervical patients at high risk of para-aortic lymph node (PALN) recurrence. Patients and Methods: From July 1999 to May 2022, a total of 115 patients with cervical cancer and high-risk features of PALN recurrence based on tumor markers, positive LNs and extensive parametrial invasion were retrospectively analyzed. All patients had received EFRT or WPRT at a dose of 39.6-45 Gy and concurrent chemotherapy. In EFRT, coverage was extended to include the para-aortic region below the level of the left renal vein or T12. Results: Twenty-eight and 87 patients underwent EFRT and WPRT, respectively. For patients who survived, the median follow-up time was 60.8 months (range 9.2-131.6 months) in the EFRT group and 115.9 months (range 16.9-212.1 months) in the WPRT group. The 5-year overall survival (OS) and pelvic, extrapelvic and PALN recurrence rates were 87.7% vs 60.8% (p=0.019), 10.9% vs 25.3% (p=0.119), 18.1% vs 45.8% (p=0.011), and 0% vs 30.4% (p=0.005), respectively, between the EFRT and WPRT groups. Multivariate analysis revealed that EFRT and 2018 FIGO stage IV disease status were significant predictors of OS and extrapelvic recurrence. Conclusion: Compared to WPRT, EFRT significantly improved OS and reduced extrapelvic and PALN recurrence in patients with cervical cancer with high-risk recurrence features.

Comparison of Oncologic Outcomes between Radical Hysterectomy and Primary Concurrent Chemoradiotherapy in Women with Bulky IB and IIA Cervical Cancer under Risk Stratification.

PURPOSE: To stratify patients according to tumor marker and histology and compare the survival outcome between radical hysterectomy (RH) and primary concurrent chemoradiotherapy (CCRT) in bulky IB and IIA cervical cancer. METHODS: A total of 442 patients with cervical cancer were enrolled in the Chang Gung Research Database from January 2002 to December 2017. Patients with squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA) ≥10 ng/mL, adenocarcinoma (AC), or adenosquamous carcinoma (ASC) were stratified into the high-risk (HR) group. The others were classified into the low-risk (LR) group. We compared oncology outcomes between RH and CCRT in each group. RESULTS: In the LR group, 5-year overall survival (OS) and recurrence-free survival (RFS) were 85.9% vs. 85.4% (p = 0.315) and 83.6% vs. 82.5% (p = 0.558) in women treated with RH (n = 99) vs. CCRT (n = 179), respectively. In the HR group, the 5-year OS and RFS were 83.2% vs. 73.3% (p = 0.164) and 75.2% vs. 59.6% (p < 0.036) in patients treated with RH (n = 128) vs. CCRT (n = 36), respectively. Regarding recurrence, locoregional recurrence (LRR) (8.1% vs. 8.6%, p = 0.812) and distant metastases (DM) (17.8% vs. 21%, p = 0.609) were similar between RH and CCRT in the LR group. However, lower LRR (11.6% vs. 26.3%, p = 0.023) but equivalent DM (17.8% vs. 21%, p = 0.609) were found for women undergoing RH compared with CCRT in the HR group. CONCLUSIONS: There were similar survival and recurrence rates between both treatment modalities in low-risk patients. Meanwhile, primary surgery with or without adjuvant radiation provides better RFS and local control in women with high-risk features. Further prospective studies are needed to confirm these findings.

In vitro antagonistic growth effects of Lactobacillus fermentum and lactobacillus salivarius and their fermentative broth on periodontal pathogens.

As lactobacilli possess an antagonistic growth property, these bacteria may be beneficial as bioprotective agents for infection control. However, whether the antagonistic growth effects are attributed to the lactobacilli themselves or their fermentative broth remains unclear. The antagonistic growth effects of Lactobacillus salivarius and Lactobacillus fermentum as well as their fermentative broth were thus tested using both disc agar diffusion test and broth dilution method, and their effects on periodontal pathogens, including Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis in vitro at different concentrations and for different time periods were also compared. Both Lactobacillus salivarius and Lactobacillus fermentum and their concentrated fermentative broth were shown to inhibit significantly the growth of Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis, although different inhibitory effects were observed for different pathogens. The higher the counts of lactobacilli and the higher the folds of concentrated fermentative broth, the stronger the inhibitory effects are observed. The inhibitory effect is demonstrated to be dose-dependent. Moreover, for the lactobacilli themselves, Lactobacillus fermentum showed stronger inhibitory effects than Lactobacillus salivarius. However, the fermentative broth of Lactobacillus fermentum showed weaker inhibitory effects than that of Lactobacillus salivarius. These data suggested that lactobacilli and their fermentative broth exhibit antagonistic growth activity, and consumption of probiotics or their broth containing lactobacilli may benefit oral health.

In vivo cytokine modulatory effects of cinnamaldehyde, the major constituent of leaf essential oil from Cinnamomum osmophloeum Kaneh.

The purpose of this study was to analyse the major compound in the leaf essential oil of Cinnamomum osmophloeum Kaneh. and to examine its in vivo toxicity and cytokine-modulatory effects. The HS-GC/MS and quantitative HPLC analyses showed the concentrations of the major compounds, cinnamaldehyde, benzaldehyde and 3-phenylpropionaldehyde, in the leaf essential oil of Cinnamomum osmophloeum to be 16.88, 1.28 and 1.70 mg/mL, respectively. Acute and sub-acute toxicity tests identified no significant changes in body weight, liver and kidney function indices, and pathology for the mice treated with up to 1 mL/kg body weight of Cinnamomum osmophloeum leaf essential oil or up to 4 mg/kg body weight of cinnamaldehyde. A murine model was established using ovalbumin (OVA)-primed Balb/C mice treated with various concentrations of Cinnamomum osmophloeum leaf essential oil or cinnamaldehyde daily for 4 weeks. The results of tests with commercial ELISA kits indicated no significant cytokine-modulatory effects in mice treated with Cinnamomum osmophloeum leaf essential oil; however, the serum concentrations of IL-2, IL-4 and IL-10, but not IFN-γ, significantly increased in animals treated with 1 mg/kg body weight of cinnamaldehyde during the 4-week period. The possibility that the other constituents act as antagonists of cinnamaldehyde cannot be excluded.

Analysis of prognostic factors and clinical outcomes in uterine cervical carcinoma with isolated para-aortic lymph node recurrence.

To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.

In vitro anti-microbial and in vivo cytokine modulating effects of different prepared Chinese herbal medicines.

The toxicity, antimicrobial and cytokine modulating effects of herbal medicines in treating periodontal diseases were evaluated in this study. Using the broth dilution method and disc agar diffusion test, in individual and combined decocted preparations, different concentrations of Ching-Wei-San and its individual herbal components, Coptidis rhizoma, Angelicae sinensis radix, Rehmanniae radixet rhizom, Moutan radicis cortex, and Cimicifuga foetida, were tested for in vitro inhibitory effects on three well-known plaque-causing bacteria, Porphyromonas gingivialis, Streptococcus sanguis, and Streptococcus mutans, and two common pathogens, Staphylococcus aureus and Escherichia coli. The cytokine modulating effects were evaluated in Balb/c mice. The results suggested that one milliliter Ching-Wei-San at the 25,000 mg/mL concentration daily for the mice had significantly high levels in the liver function indexes in the 3-day acute toxicity test and in both the liver and kidney function indexes in the 28-day subacute toxicity test (P<0.01). The 250 mg/mL Ching-Wei-San is comparable to 250 mg/mL of tetracycline, and had similar inhibitory effects on the tested bacteria. Coptidis rhizoma (62.5 mg/mL) was the only individual herbal component to show 100% inhibitory effects. The mean cytokine ratios of IL-2, IL-4, IFN-gamma, and TNF-alpha in Balb/c mice treated with individual herbal components were shown to be different from each other. Ching-Wei-San modulated the immunity of mice, up-regulated IL-2, IL-4 and TNF-alpha, but down-regulated IFN-gamma. The effects of none of the individual herbal components alone can substitute for the cumulative effect of Ching-Wei-San.

In vitro antagonistic growth effects of Lactobacillus fermentum and Lactobacillus salivarius and their fermentative broth on periodontal pathogens

As lactobacilli possess an antagonistic growth property, these bacteria may be beneficial as bioprotective agents for infection control. However, whether the antagonistic growth effects are attributed to the lactobacilli themselves or their fermentative broth remains unclear. The antagonistic growth effects of Lactobacillus salivarius and Lactobacillus fermentum as well as their fermentative broth were thus tested using both disc agar diffusion test and broth dilution method, and their effects on periodontal pathogens, including Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalisin vitro at different concentrations and for different time periods were also compared. Both Lactobacillus salivarius and Lactobacillus fermentum and their concentrated fermentative broth were shown to inhibit significantly the growth of Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis, althoughdifferent inhibitory effects were observed for different pathogens. The higher the counts of lactobacilli and the higher the folds of concentrated fermentative broth, the stronger the inhibitory effects are observed. The inhibitory effect is demonstrated to be dose-dependent. Moreover, for the lactobacilli themselves, Lactobacillus fermentum showed stronger inhibitory effects than Lactobacillus salivarius. However, the fermentative broth of Lactobacillus fermentum showed weaker inhibitory effects than that of Lactobacillus salivarius. These data suggested that lactobacilli and their fermentative broth exhibit antagonistic growth activity, and consumption of probiotics or their broth containing lactobacilli may benefit oral health.

Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo.

OBJECTIVES: Five CAPE-like compounds, namely caffeic acid phenethyl ester (CAPE), methyl caffeate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl dimethyl caffeate (PEDMC) and phenethyl 3-(4-bromophenyl)acrylic (BrCAPE) were tested for their anti-HIV replication in vitro and immune modulation effects in vivo. METHODS: Short-term cytotoxicity was assessed by Trypan Blue stain and MTT assay. For antiviral assays, M-tropic (strain JRCSF), T-tropic (strain NL-4-3) and dual tropic (strain 89.6) HIV isolates were used in peripheral blood mononuclear cell (PBMC) culture. RESULTS: None of these CAPE-like compounds showed significant cytotoxicity in the treatment of PBMCs. By P24 EIA tests, CAPE, MC and EC significantly inhibited HIV replication in PBMC cells, but PEDMC and BrCAPE showed only slightly inhibitory effects. The in vivo modulatory effects on six cytokines [interleukin (IL)-2, IL-4, IL-6, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and soluble Fas] were analysed. BALB/c mice treated with different doses or not treated with these CAPE-like chemicals showed that cytokines were increased to different extents by the different treatments. However, the concentrations of IL-6 and GM-CSF were not significantly affected by administration of any of these compounds (P > 0.05). CONCLUSIONS: The different effects of treatments on anti-HIV replication and cytokine modulation suggested that these compounds affect virological and immunological response via different mechanisms. The virological and immunological mechanisms and response to these treatments need to be elaborated in further studies in order to derive the structural features of more effective compounds. Since neither death nor pathological change in the mice were observed in this study, these CAPE-like compounds are worth studying further as potential chemotherapy agents for anti-HIV infection and cytokine modulation.