Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26–87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients’ performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78–7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79–6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12–2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.     

Prevention of renal ischemia/reperfusion-induced injury in rats by leflunomide

OBJECTIVE: There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of leflunomide, an isoxazole derivative and a unique immunomodulatory agent, in I/R-induced renal injury in rats. METHODS: Forty female Sprague-Dawley rats were divided equally into four groups: (I) control (only leflunomide 10 mg/kg, intragastrically treated); (II) sham operated (only unilateral nephrectomy); (III) I/R; and (IV) leflunomide (10 mg/kg for two doses prior to experiment) plus I/R groups. In groups III and IV, after unilateral nephrectomy, the rats were subjected to 60 min of left renal pedicle occlusion, followed by 6 h of reperfusion. At the end of the reperfusion period, rats were killed and kidneys and blood were removed. Catalase, myeloperoxidase and xanthine oxidase activities, and malondialdehyde, nitric oxide and protein carbonyl levels were determined in renal tissue. Serum creatinine, blood urea nitrogen and aspartate aminotransferase were measured for the evaluation of renal function. In histopathological examination, renal damage was scored 0-3. RESULTS: Group III animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with leflunomide markedly attenuated renal dysfunction, morphological alterations, reduced elevated oxidative stress products levels and restored the depleted renal antioxidant enzyme. CONCLUSION: The findings imply that oxygen radicals play a causal role in I/R-induced renal injury, and leflunomide exerts renoprotective effects probably by the radical scavenging and antioxidant activities with immunomodulatory effect.     

Cytotoxic effects of halogen- and light-emitting diode-cured compomers on human pulp fibroblasts

Objective.  The aim of this study was to determine the cytotoxic effects of three different compomers (Dyract AP, Compoglass, and Hytac) cured using a halogen light-curing unit (LCU) and a light-emitting diode (LED) LCU on human pulp fibroblasts.
Methods.  Specimens of three compomers were added to human pulp fibroblast cultures. Cytotoxicity was evaluated over 96 h using the agar overlay method.
Results.  All three compomers tested were found to be moderately cytotoxic to human pulp fibroblasts, regardless of whether they were cured using halogen or LED LCUs. The decolorization zone of Hytac was significantly larger than those of the other compomers tested ( P  < 0.05). Dyract AP and Compoglass specimens showed greater decolorization when cured with LED than with halogen LCUs ( P  < 0.05).
Conclusion.  Compomers are potentially toxic to human pulp fibroblasts, and the type of curing unit may affect compomer toxicity.     

ACUTE EFFECT OF ENDOTHELIN-1 ON LUNG OEDEMA INDUCED BY ALPHA-NAPHTHYLTHIOUREA (ANTU)

Alpha-naphthylthiourea when injected intraperitoneally to rats (10mgkg⁻¹i.p.) produced lung oedema as indicated by an increase in lung weight/body ratio and pleural effusion reaching a maximum within 4 hours. Prior intravenous single bolus injection of endothelin-1 elicited a significant and dose-dependent inhibition in both parameters. However, prior i.v. injection of angiotensin II using relatively higher doses did not alter the oedema-producing effect of alpha-naphthylthiourea indicating a characteristic for endothelin-1. The inhibitory effect of endothelin-1 on pleural effusion is more prominent than lung weight/body weight ratio. The resolution of lung oedema by single bolus i.v. injection of endothelin-1 is probably due to the acute long-lasting and potent vasoconstrictor effect of the peptide and its large accumulation in lung tissue. Phosphoramidon, an inhibitor of endothelin converting enzyme, did not alter the oedema producing effect of alpha-naphthylthiourea indicating the lack of the participation of endothelin-peptide cascade to this pathological event. Bosentan, a non-selective receptor blocker of endothelin-1, did not inhibit the preventive effect of the peptide against alpha-naphthylthiourea-induced lung oedema. Possible mechanisms of the acute effect of endothelin-1 on lung oedema are discussed.     

P-Wave Duration and Dispersion in Patients with Metabolic Syndrome

Background: Metabolic syndrome (MS) has been reported to be associated with an increased risk of atrial fibrillation (AF). The aim of this study was to investigate P-wave dispersion (PWD) in patients with MS.
Methods: The study population included 66 patients with MS (21 men, 45 women; mean age, 49.7 ± 9.1 years) and 63 control subjects without MS (26 men, 37 women; mean age, 47.0 ± 10.6 years). The diagnosis of MS was based on the National Cholesterol Education Program Adult Treatment Panel III criteria. A 12-lead electrocardiogram was recorded for each subject. The difference between maximum and minimum P-wave duration was calculated and defined as PWD. An echocardiographic examination was also performed for each subject.
Results: Maximum P-wave duration and PWD were found to be significantly higher in patients with MS compared with the control subjects (Maximum P-wave duration: 113.5 ± 9.7 ms vs 101.0 ± 8.1 ms, PWD: 37.8 ± 7.6 vs 23.3 ± 5.9, respectively, P < 0.001 for both). However, there was no statistically significant difference between two groups regarding minimum P-wave duration (75.6 ± 6.9 ms vs 77.6 ± 7.8 ms, respectively, P = 0.18). In addition, PWD was positively correlated with age, body mass index, waist circumference, systolic and diastolic blood pressure, triglyceride level, deceleration time, isovolumetric relaxation time and negatively correlated with high-density lipoprotein cholesterol level and early-to-late diastolic velocity ratio .
Conclusion: We have shown that patients with MS have higher PWD, indicating increased risk for AF, compared to the control subjects without MS.     

Polyenylphosphatidylcholine pretreatment ameliorates ischemic acute renal injury in rats

AIM: Polyenylphosphatidycholine has been demonstrated to have antioxidant, cytoprotective and anti-inflammatory effects. Whether polyenylphosphatidycholine pretreatment affects ischemia/reperfusion-induced renal damage in vivo is not known and was investigated here in rats. METHODS: Forty female Sprague-Dawley rats were divided into three groups. Group 1 (n = 10) was given saline (control, sham operated). Group 2 (n = 15) were given saline, and Group 3 (n = 15) were given polyenylphosphatidycholine (100 mg/day for 10 days prior to experiment). Groups 2 and 3 were subjected to bilateral renal ischemia (60 min) followed by reperfusion (6 h). After the reperfusion period, the rats were sacrificed and kidney tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde and myeloperoxidase levels, plasma aspartate aminotransferase, blood urea nitrogen and creatinine concentrations, and nuclear factor kappa beta expression were determined. RESULTS: Serum levels of aspartate aminotransferase, blood urea nitrogen and creatinine were significantly decreased (P < 0.05) in the treatment group compared to those in the ischemic group. There were significant differences between treatment and ischemic groups regarding the tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde, and myeloperoxidase levels (P < 0.05). In addition, polyenylphosphatidycholine pretreatment reduced nuclear factor kappa beta expression in ischemic kidney tissue. Kidneys obtained from rats pretreated with polyenylphosphatidycholine demonstrated marked reduction of the histological features of renal injury compared to kidneys obtained from Group 2 rats, including a little vacuolization, pyknosis and necrosis. CONCLUSIONS: Polyenylphosphatidycholine pretreatment provided significant protection against ischemia/reperfusion injury to the kidney. This treatment could be therapeutic in kidney transplantation and other conditions associated with ischemia/reperfusion injury to the kidney.