Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy.

Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation-induced intestinal syndromes in survivors of pelvic cancer.

Methods And Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers.

Remarkable effects of infliximab on severe radiation-induced side effects in a patient with uterine cervical cancer: a case report.

Pelvic radiotherapy is a powerful treatment for a broad range of cancers, including gynecological, prostate, rectal, and anal cancers. Despite improvements in the delivery of ionizing beams, damage to non-cancerous tissue can cause long-term effects that are potentially severe, affecting quality of life and daily function. There is an urgent need for new strategies to treat and reverse the side effects of pelvic radiotherapy without compromising the antitumor effect.

Low-grade intestinal inflammation two decades after pelvic radiotherapy.

Background: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not.

A Fiber-Rich Diet and Radiation-Induced Injury in the Murine Intestinal Mucosa.

Dietary fiber is considered a strong intestinal protector, but we do not know whether dietary fiber protects against the long-lasting mucosal damage caused by ionizing radiation. To evaluate whether a fiber-rich diet can ameliorate the long-lasting pathophysiological hallmarks of the irradiated mucosa, C57BL/6J mice on a fiber-rich bioprocessed oat bran diet or a fiber-free diet received 32 Gray in four fractions to the distal colorectum using a linear accelerator and continued on the diets for one, six or 18 weeks. We quantified degenerating crypts, crypt fission, cell proliferation, crypt survival, macrophage density and bacterial infiltration.

A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy.

Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed.

Dietary Fiber and the Hippocampal Neurogenic Niche in a Model of Pelvic Radiotherapy.

We sought to determine whether radiation to the colorectum had an impact on parameters of hippocampal neurogenesis and, if so, whether it could be modulated by a fiber-rich diet. Male C57BL/6J mice were fed a diet containing bioprocessed oat bran or a fiber-free diet, starting two weeks before colorectal irradiation with 4 fractions of 8 Gray or sham-irradiation. Diets were then continued for 1, 6 or 18 weeks, whereafter parameters of hippocampal neurogenesis were analyzed and correlated to serum cytokine levels.

Role of dietary fiber in safeguarding intestinal health after pelvic radiotherapy.

Purpose Of Review: Damage to healthy bowel tissue during pelvic radiotherapy can produce devastating and life-long changes in bowel function. The surging interest in microbiota and its importance for our wellbeing has generated a bulk of research highlighting how the food we consume impacts bowel health and disease. Dietary fiber is known to promote bowel health, yet there is a limited number of studies on dietary fiber in connection to pelvic radiotherapy.

Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy.

Background: The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the 'excessive mucus discharge' syndrome after pelvic radiotherapy for gynaecological cancer.

Methods And Materials: From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma.

Dietary Oat Bran Reduces Systemic Inflammation in Mice Subjected to Pelvic Irradiation.

Patients undergoing radiotherapy to treat pelvic-organ cancer are commonly advised to follow a restricted fiber diet. However, reducing dietary fiber may promote gastrointestinal inflammation, eventually leading to deteriorated intestinal health. The goal of this study was to evaluate the influence of dietary fiber on radiation-induced inflammation.

Long-term mucosal injury and repair in a murine model of pelvic radiotherapy.

Chronic intestinal injury after pelvic radiotherapy affects countless cancer survivors worldwide. A comprehensive understanding of the long-term injury dynamics is prevented in available animal models. With linear accelerators that are used to treat cancer in patients, we irradiated a small volume encompassing the colorectum in mice with four fractions of 8 Gy per fraction.

Intake of citrus fruits and vegetables and the intensity of defecation urgency syndrome among gynecological cancer survivors.

Background: Despite the experimental evidence that certain dietary compounds lower the risk of radiation-induced damage to the intestine, clinical data are missing and dietary advice to irradiated patients is not evidence-based.

Materials And Methods: We have previously identified 28 intestinal health-related symptoms among 623 gynaecological-cancer survivors (three to fifteen years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five radiation-induced survivorship syndromes: defecation-urgency syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge and blood discharge.

[Differing dietary advice are given to gynaecological and prostate cancer patients receiving radiotherapy in Sweden].

Preclinical studies indicate that an optimal diet during pelvic radiotherapy may be able to prevent radiation-induced survivorship diseases that diminish cancer survivors' intestinal health. We do not yet know what this optimal diet might be because scientific studies needed to determine what dietary advice might best be given to patients during treatment. Oncology clinics in Sweden were contacted to determine the nature of dietary advice given to gynaecological and prostate cancer patients at each clinic before, during and after radiotherapy.

Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.

Purpose: To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future.

Material And Methods: From a larger group of gynecological cancer survivors followed-up 2-14 years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome.

Elastase as a potential biomarker for radiation-induced gut wall injury of the distal bowel in an experimental mouse model.

Background And Purpose: Traditionally, elastase has been used to study exocrine activity of the pancreas in patients with chronic pancreatitis and cystic fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with inflammatory bowel disease. The aim of the study was to find out whether elastase and calprotectin could be used as inflammatory markers for radiation-induced gut wall injury of the distal bowel.

Material And Methods: Adult male mice were exposed to two, three, or four fractions of 6 Gy or 8 Gy irradiation to the sigmoid and rectum of the large bowel, using a linear accelerator.

A role for endothelial cells in radiation-induced inflammation.

Purpose: To unravel the role of the vasculature in radiation-induced brain tissue damage.

Materials And Methods: Postnatal day 14 mice received a single dose of 10 Gy cranial irradiation and were sacrificed 6 h, 24 h or 7 days post-irradiation. Endothelial cells were isolated from the hippocampus and cerebellum using fluorescence-activated cell sorting, followed by cell cycle analysis and gene expression profiling.

Exercise in Adulthood after Irradiation of the Juvenile Brain Ameliorates Long-Term Depletion of Oligodendroglial Cells.

Cranial radiation severely affects brain health and function, including glial cell production and myelination. Recent studies indicate that voluntary exercise has beneficial effects on oligodendrogenesis and myelination. Here, we hypothesized that voluntary running would increase oligodendrocyte numbers in the corpus callosum after irradiation of the juvenile mouse brain.

A novel mouse model of radiation-induced cancer survivorship diseases of the gut.

A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival.

Late radiation-induced bowel syndromes, tobacco smoking, age at treatment and time since treatment - gynecological cancer survivors.

Background: It is unknown whether smoking; age at time of radiotherapy or time since radiotherapy influence the intensity of late radiation-induced bowel syndromes.

Material And Methods: We have previously identified 28 symptoms decreasing bowel health among 623 gynecological-cancer survivors (three to twelve years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five separate late bowel syndromes through factor analysis.

Identifying radiation-induced survivorship syndromes affecting bowel health in a cohort of gynecological cancer survivors.

Background: During radiotherapy unwanted radiation to normal tissue surrounding the tumor triggers survivorship diseases; we lack a nosology for radiation-induced survivorship diseases that decrease bowel health and we do not know which symptoms are related to which diseases.

Methods: Gynecological-cancer survivors were followed-up two to 15 years after having undergone radiotherapy; they reported in a postal questionnaire the frequency of 28 different symptoms related to bowel health. Population-based controls gave the same information.

Toward Restored Bowel Health in Rectal Cancer Survivors.

As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms.

Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior.

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique.

Differential response of glial fibrillary acidic protein-positive astrocytes in the rat prefrontal cortex following ethanol self-administration.

Background: Prefrontal cortex (PFC) dysfunction is believed to contribute to the transition from controlled substance use to abuse. Because astrocytes have been suggested to play a key role in the development and maintenance of drug-seeking behaviors, we sought to determine whether PFC astrocytes are affected by ethanol (EtOH) self-administration.

Methods: EtOH consumption was modeled in rats by 3 self-administration paradigms where EtOH was made concurrently available with water in the home cage either continuously (CEA) or intermittently (IEA).

Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration.