An Oligomeric Sulfated Hyaluronan and Silk-Elastinlike Polymer Combination Protects against Murine Radiation Induced Proctitis

Semisynthetic glycosaminoglycan ethers (SAGEs) are short, sulfated hyaluronans which combine the natural properties of hyaluronan with chemical sulfation. In a murine model, SAGEs provide protection against radiation induced proctitis (RIP), a side effect of lower abdominal radiotherapy for cancer. The anti-inflammatory effects of SAGE have been studied in inflammatory diseases at mucosal barrier sites; however, few mechanisms have been uncovered necessitating high throughput methods. SAGEs were combined with silk-elastinlike polymers (SELPs) to enhance rectal accumulation in mice. After high radiation exposure to the lower abdominal area, mice were followed for 3 days or until they met humane endpoints, before evaluation of behavioral pain responses and histological assessment of rectal inflammation. RNA sequencing was conducted on tissues from the 3-day cohort to determine molecular mechanisms of SAGE–SELP. After 3 days, mice receiving the SAGE–SELP combination yielded significantly lowered pain responses and amelioration of radiation-induced rectal inflammation. Mice receiving the drug–polymer combination survived 60% longer than other irradiated mice, with a fraction exhibiting long term survival. Sequencing reveals varied regulation of toll like receptors, antioxidant activities, T-cell signaling, and pathways associated with pain. This investigation elucidates several molecular mechanisms of SAGEs and exhibits promising measures for prevention of RIP.

Radiotherapy-Induced Digestive Injury: Diagnosis, Treatment and Mechanisms

Radiotherapy is one of the main therapeutic methods for treating cancer. The digestive system consists of the gastrointestinal tract and the accessory organs of digestion (the tongue, salivary glands, pancreas, liver and gallbladder). The digestive system is easily impaired during radiotherapy, especially in thoracic and abdominal radiotherapy. In this review, we introduce the physical classification, basic pathogenesis, clinical characteristics, predictive/diagnostic factors, and possible treatment targets of radiotherapy-induced digestive injury. Radiotherapy-induced digestive injury complies with the dose-volume effect and has a radiation-based organ correlation. Computed tomography (CT), MRI (magnetic resonance imaging), ultrasound (US) and endoscopy can help diagnose and evaluate the radiation-induced lesion level. The latest treatment approaches include improvement in radiotherapy (such as shielding, hydrogel spacers and dose distribution), stem cell transplantation and drug administration. Gut microbiota modulation may become a novel approach to relieving radiogenic gastrointestinal syndrome. Finally, we summarized the possible mechanisms involved in treatment, but they remain varied. Radionuclide-labeled targeting molecules (RLTMs) are promising for more precise radiotherapy. These advances contribute to our understanding of the assessment and treatment of radiation-induced digestive injury.

Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol

Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.