Radiation Proctitis: Current Strategies in Management

Radiation proctitis is a known complication following radiation therapy for pelvic malignancy. The majority of cases are treated nonsurgically, and an understanding of the available modalities is crucial in the management of these patients. In this paper, we focus on the current treatments of radiation proctitis

The NF-κB Inhibitor Curcumin Blocks Sepsis-Induced Muscle Proteolysis

We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-κB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-κB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-κB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting

In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes

EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-α (TNF-α) and proteolysis-inducing factor (PIF). EPA (50 μM) or curcumin (10 μg ml−1) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 μg ml−1). In response to TNF-α (25 ng ml−1)-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-α, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-α, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-α and PIF significantly reduced myotube diameter from 17 to 13 μm for TNF-α (23.5%) and 15 μm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass

Biological welding – novel technique in the treatment of esophageal metaplasia

Introduction: Biological welding – controlled action of high frequency current on living tissues, which leads to their structural changes and weld formation – connection with unique biological properties (strength, high elasticity, insensitivity to microbial infection, stimulating effect on the regeneration process, speed and quality which surpasses the normal uncomplicated healing) [22]. This method is used in various fields of surgery, but at the moment there is no data on its use in case of esophageal cylindrocellular (intestinal) metaplasia (further esophageal metaplasia or Barrett’s esophagus). Objective: The goal of this study is to evaluate biologic welding as a treatment option for patients with Barrett’s esophagus. Materials and methods: Single-center retrospective review of patients with short-segment Barrett’s esophagus and metaplasia were treated by argon plasma coagulation (APC) or Paton’s welding. This was followed by Nissen fundoplication. Primary outcome of this study was mucosal healing with morphological confirmation of the absence of metaplasia. The groups included patients with a short segment of the esophagus Barrett’s C2-3M3-4 (Prague Classification 2004) and high dysplasia without nodule formation in combination with hiatal hernia (VI World Congress of the International Society for Esophageal Diseases; ISED) [23–25]). Results: A total of 49 patients were included in the study with 25 patients treated by APC laser and 24 by biowelding. Four patients (16.0%) in the APC group developed stenosis and 5 patients (20.0%) developed recurrence compared to none in the biowelding group. Patients in the biowelding group had a significantly faster rate of mucosal healing leading to faster progression to Nissen fundoplication (at average 53 days) compared to APC laser group (surgery at 115 days). Conclusions: Biological welding of Paton’s is a safe and effective treatment option for patients with esophageal metaplasia

Antireflux surgery is required after endoscopic treatment for Barrett’s esophagus

Introduction: Barrett’s esophagus is an acquired condition that develops as a result of transformation of normal stratified squamous epithelium in the lower part of the esophagus into columnar epithelium. Barrett’s esophagus is considered to be a complication of gastroesophageal reflux disease (GERD). Various endoscopic techniques have been shown to be successful in the treatment of this condition. However, long-term success in preventing further esophageal dysplasia is not clear. Biological welding consists in the application of controlled high-frequency current on living tissues and has been used to stop gastrointestinal bleeding, similarly to the APC technique which involves ablation of small intestinal metaplasia of the esophageal mucosa. Aim: The goal of this study was to evaluate the effectiveness of endoscopic techniques in the treatment of Barrett’s esophagus and verify the need for a subsequent surgical intervention in patients with GERD complicated by Barrett’s esophagus. Material and methods: Patients with Barrett’s esophagus C1-3M2-4 (Prague classification from 2004) and high dysplasia without nodules, as well as patients with confirmed GERD without hiatal hernia, were included in this study. Endoscopic treatment was performed with the use of argonoplasmic coagulation (APC) and high-frequency welding of living tissues (HFW). After the examination the patients were re-examined. Patients with recurrence of metaplasia and high DeMeester score (˃ 100) underwent antireflux surgery – crurography and Nissen fundoplication with creation of a soft and short cuff.Results: A total of 89 patients were included in the study, 81 of whom were reexamined after ablation of Barrett’s esophagus.In 12 patients, a recurrence of intestinal metaplasia resembling the small intestine was identified. Implementation of two-stage treatment was required for 9 patients – it involved a second procedure of ablation of the esophagus, followed by antireflux surgery. Surgical treatment was refused by 3 patients, who underwent only the second ablation procedure. All patients received drug therapy, consisting of prokinetics and proton pump inhibitors. Esophageal pH monitoring was repeated 3 months after surgery, showing normalization of the DeMeester score. As a result, the patients experienced no complaints such as heartburn, chest pain or dysphagia, which significantly improved their quality of life. Esophagogastroduodenoscopy and biopsy of the mucous membrane of the lower third of the esophagus were performed in accordance with the Seattle Protocol. After examining histological specimens, no regions of metaplasia were identified. Conclusion: Antireflux surgery is required as a part of the treatment for Barrett’s esophagus, which prevents further dysplasia and development of esophageal cancer