Gastrointestinal Acute Syndrome Research Articles

Methods for induction and assessment of intestinal permeability in rodent models of radiation injury.

Ionizing radiation (IR) is a significant contributor to the contemporary market of energy production and an important diagnostic and treatment modality. Besides having numerous useful applications, it is also a ubiquitous environmental stressor and a potent genotoxic and epigenotoxic agent, capable of causing substantial damage to organs and tissues of living organisms. The gastrointestinal (GI) tract is highly sensitive to IR. This problem is further compounded by the fact that there is no FDA-approved medication to mitigate acute radiation-induced GI syndrome. Therefore, establishing the animal model for studying IR-induced GI-injury is crucially important to understand the harmful consequences of intestinal radiation damage. Here, we discuss two different animal models of IR-induced acute gastrointestinal syndrome and two separate methods for measuring the magnitude of intestinal radiation damage.

An Active Fraction of Trillium tschonoskii Promotes the Regeneration of Intestinal Epithelial Cells After Irradiation.

Despite significant scientific advances toward the development of safe and effective radiation countermeasures, no drug has been approved for use in the clinic for prevention or treatment of radiation-induced acute gastrointestinal syndrome (AGS). Thus, there is an urgent need to develop potential drugs to accelerate the repair of injured intestinal tissue. In this study, we investigated that whether some fractions of Traditional Chinese Medicine (TCM) have the ability to regulate intestinal crypt cell proliferation and promotes crypt regeneration after radiation. By screening the different supplements from a TCM library, we found that an active fraction of the rhizomes of Trillium tschonoskii Maxim (TT), TT-2, strongly increased the colony-forming ability of irradiated rat intestinal epithelial cell line 6 (IEC-6) cells. TT-2 significantly promoted the proliferation and inhibited the apoptosis of irradiated IEC-6 cells. Furthermore, in a small intestinal organoid radiation model, TT-2 promoted irradiated intestinal organoid growth and increased Lgr5+ intestinal stem cell (ICS) numbers. More importantly, the oral administration of TT-2 remarkably enhanced intestinal crypt cell proliferation and promoted the repair of the intestinal epithelium of mice after abdominal irradiation (ABI). Mechanistically, TT-2 remarkably activated the expression of ICS-associated and proliferation-promoting genes and inhibited apoptosis-related gene expression. Our data indicate that active fraction of TT can be developed into a potential oral drug for improving the regeneration and repair of intestinal epithelia that have intestinal radiation damage.

Acute Radiation-induced GI-ARS and H-ARS in a Canine Model of Mixed Neutron/Gamma Relative to Reference Co-60 Gamma Radiation: A Retrospective Study.

Studies performed decades ago in the canine and nonhuman primate established the dose response relationships for the hematopoietic acute radiation syndrome in response to mixed neutron/gamma, x-radiation, and Co gamma radiation. There were no published studies that determined the dose response relationships for the gastrointestinal acute radiation syndrome in response to either noted radiation quality. This analysis of a retrospective, unpublished study provided the dose response relationships in a canine model for the acute gastrointestinal syndrome relative to the acute hematopoietic syndrome due to mixed neutron/gamma radiation. Canines were exposed to total-body, steady state, bilateral, 0.40 Gy min, mixed neutron/gamma (5.4:1) radiation from a TRIGA reactor. The average neutron/gamma energy (MeV) was 0.85/0.9, and exposure was reported as midline tissue dose. Medical management was not administered. The mixed neutron/gamma exposure resulted in an estimated LD50/6 of 2.83 Gy [2.76, 2.94] and LD50/30 of 2.16 Gy [2.01, 2.24] for the GI- and H-ARS respectively. The mean survival times for decedents after mixed neutron/gamma exposure approximate to the LD50/6 were 8.5 d, 10.5 d, and 4 d for 2.75 Gy, 2.80 Gy, 3.00, and 3.12 Gy exposures, respectively. The mean survival times for decedents for mixed neutron/gamma exposure approximate to the LD50/30 were 21.3 d and 15.6 d for 2.00 Gy and 2.25 Gy, respectively. Furthermore, the dose response relationships for the acute hematopoietic syndrome due to mixed neutron/gamma exposure (0.85/0.9 MeV; 5.4:1) resulted in an estimated relative biological effectiveness of 1.2 as compared with reference Co gamma radiation.

Me6TREN targets β-catenin signaling to stimulate intestinal stem cell regeneration after radiation.

Background: Acute gastrointestinal syndrome (AGS) is one of the most severe clinical manifestations after exposure to high doses of radiation, and is life-threatening in radiological emergency scenarios. However, an unmet challenge is lacking of an FDA-approved drug that can ameliorate the damage of radiation-exposed intestinal tissues and accelerate the regeneration of injured epithelia. In this study, we investigated whether the small molecule Me6TREN (Me6) can regulate intestinal stem cell (ISC) proliferation and promote crypt regeneration after irradiation.Methods: Lethally irradiated mice were administered with Me6 or PBS to study the survival rate, and sections of their small intestine were subjected to immunostaining to evaluate epithelial regeneration. An intestinal organoid culture system was employed to detect the role of Me6 in organoid growth and ISC proliferation. We further investigated the key signaling pathways associated with Me6 using microarray, western blotting, and RNA interference techniques.Results: We identified the small molecule Me6 as a potent intestinal radiation countermeasure. Systemic administration of Me6 significantly improved ISC and crypt cell regeneration and enhanced the survival of mice after high doses of radiation. Using an in vitro intestinal organoid culture system, we found that Me6 not only induced ISC proliferation but also increased the budding rate of intestinal organoids under unirradiated and irradiated conditions. Me6 remarkably activated the expression of ISC-associated and proliferation-promoting genes, such as Ascl2, Lgr5, Myc, and CyclinD1. Mechanistically, Me6 strongly stimulated the phosphorylation of β-catenin at the S552 site and increased the transcriptional activity of β-catenin, a key signaling pathway for ISC self-renewal and proliferation. This is further evidenced by the fact that knockdown of β-catenin abolished the effect of Me6 on intestinal organoid growth in vitro and crypt regeneration in irradiated mice.Conclusion: The small molecule Me6TREN induced ISC proliferation, enhanced intestinal organoid growth in vitro, and promoted intestinal tissue regeneration after radiation injury by activating β-catenin signaling.

Triptan and ergotamine overdoses in the United States: Analysis of the National Poison Data System.

To examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS). This was a 5-year retrospective cross-sectional study (2014-2018) using the NPDS. Demographics, exposure characteristics, and outcomes were described. Univariate logistic regression was used to estimate the odds ratio (OR) for major effect or death. A multivariable logistic regression model with inclusion criteria of p < 0.1 in univariate analysis was implemented with backwards selection. In this population (n = 1,489), multiple exposure was most common (n = 1,145). The mean age was 31.2 years and 1,197 (80.4%) participants were female. Major effects from a single exposure were seen in <1% with no recorded deaths. Triptan ingestion (n = 328) resulted in hypertension (14%), tachycardia (10.7%), drowsiness (11%), nausea (6.4%), vomiting (4.6%), vertigo (4%), chest pain (3.7%), and diaphoresis (2.4%). Ergotamine ingestion (n = 16) resulted in abdominal pain (16%), vomiting (12.5%), numbness (12.5%), nausea (6.3%), diarrhea (6.3%), and vertigo (6.3%). No clinical effect was seen in 90 (26.2%). No cases met Hunter criteria for serotonin syndrome. There is risk of major event or death due to age (OR 1.02; 95% confidence interval [CI] 1.01-1.04; p = 0.004), multiple product exposure (OR 9.50; 95% CI 2.29-39.48; p = 0.002), and concomitant overdose with benzodiazepines (OR 1.71; 95% CI 1.05-2.78; p = 0.032) or tricyclic antidepressants (OR 3.16; 95% CI 1.88-5.31; p < 0.001). The risk of major effect or death was low and predicted by age, multiple product exposure, and concomitant benzodiazepine or tricyclic antidepressant. The triptan toxidrome consists of hypertension, tachycardia, and drowsiness. The toxic effects of ergotamine are acute gastrointestinal syndrome with vertigo and numbness. No cases of serotonin syndrome were seen.

The Ham and Eggs Plant, Lantana camara

The Ham and Eggs Plant, Lantana camara

An amino acid mixture mitigates radiation-induced gastrointestinal toxicity.

Electrolyte and nutrient absorption occur in villous epithelial cells. Radiation often results in reduced electrolyte and nutrient absorption, which leads to gastrointestinal toxicity. Therefore, the authors studied: (1) radiation-induced changes in glucose and amino acid absorption across ileal tissues and (2) the effect of amino acid mixtures on absorptive capacity. NIH Swiss mice were irradiated (0, 1, 3, 5, or 7 Gy) using a ¹³⁷Cs source at 0.9 Gy min⁻¹. Transepithelial short circuit current (I(sc)), dilution potential, and isotope flux determinations were made in Ussing chamber studies and correlated to plasma endotoxin and IL-1β levels. Amino acids that increased electrolyte absorption and improved mucosal barrier functions were used to create a mitigating amino acid mixture (MAAM). The MAAM was given to mice via gastric gavage; thereafter, body weight and survival were recorded. A significant decrease in basal and glucose-stimulated sodium absorption occurred after 0, 1, 3, 5, and 7 Gy irradiation. Ussing chamber studies showed that paracellular permeability increased following irradiation and that the addition of glucose resulted in a further increase in permeability. Following irradiation, certain amino acids manifested decreased absorption, whereas others were associated with increased absorption. Lysine, aspartic acid, glycine, isoleucine, threonine, tyrosine, valine, tryptophan, and serine decreased plasma endotoxins were selected for the MAAM. Mice treated with the MAAM showed increased electrolyte absorption and decreased paracellular permeability, IL-1β levels, and plasma endotoxin levels. Mice treated with MAAM also had increased weight gain and better survival following irradiation. The MAAM has immediate potential for use in mitigating radiation-induced acute gastrointestinal syndrome.

Delta-Tocotrienol Protects Mice from Radiation-Induced Gastrointestinal Injury

We recently demonstrated that natural delta-tocotrienol (DT3) significantly enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone marrow cells from radiation-induced damage through Erk activation-associated mTOR survival pathways. Here, we further evaluated the effects and mechanisms of DT3 on survival of radiation-induced mouse acute gastrointestinal syndrome. DT3 (75-100 mg/kg) or vehicle was administered as a single subcutaneous injection to CD2F1 mice 24 h before 10-12 Gy (60)Co total-body irradiation at a dose rate of 0.6 Gy/min and survival was monitored. In a separate group of mice, jejunum sections were stained with hematoxylin and eosin and the surviving crypts in irradiated mice were counted. Apoptosis in intestinal epithelial cells was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and bacterial translocation from gut to heart, spleen and liver in irradiated mice were evaluated. DT3 (75 mg/kg) significantly enhanced survival in mice that received 10, 10.5, 11 or 12 Gy TBI. Administration of DT3 protected intestinal tissue, decreased apoptotic cells in jejunum and inhibited gut bacterial translocation in irradiated mice. Furthermore, DT3 significantly inhibited radiation-induced production of pro-inflammatory factors interleukin-1β and -6 and suppressed expression of protein tyrosine kinase 6 (PTK6), a stress-induced kinase that promotes apoptosis in mouse intestinal cells. Our data demonstrate that administration of DT3 protected mice from radiation-induced gastrointestinal system damage.

Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing, and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources, and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data, the authors have generated dose response data in adult male mice maintained under identical conditions and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow, and lung) in the surviving mice. Lethal dose (LD(30), LD(50), and LD(70)) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. These data can be used to aid the design of good laboratory practice (GLP)-compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure.

The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for efficacy and interaction during the concomitant evolution of acute and delayed key organ-specific subsyndromes.

The Acute Gastrointestinal Subsyndrome of the Acute Radiation Syndrome

The development of medical countermeasures against the acute gastrointestinal subsyndrome of the acute radiation syndrome in humans requires well characterized and validated animal models. These models must adhere to the criteria of the U.S. Food and Drug Administration's Animal Rule and consider the natural history and clinical context of the human radiation response and treatment in the nuclear terrorist scenario. The models must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity, including concurrent damage in other organs, such as the bone marrow, that may contribute to the overall mortality and morbidity. There are no such models of the gastrointestinal syndrome in response to total-body irradiation in the nonhuman primate. Herein, these parameters are defined for the rhesus macaque exposed to potentially lethal doses of radiation and administered medical management. Rhesus macaques (n = 69) were exposed bilaterally to 6 MV linear accelerator-derived photon total body irradiation to midline tissue (thorax) doses ranging from 10.0 to 14.0 Gy at 0.80 Gy min(-1). Following irradiation, all animals were administered supportive care consisting of fluids, anti-emetics, anti-diarrheal medication, antibiotics, blood transfusions, analgesics, and nutrition. The primary endpoint was survival at 15 d post-irradiation. Secondary endpoints included indices of dehydration, diarrhea, weight loss, hematological parameters, cellular histology of the small and large intestine, and mean survival time of decedents. Mortality within the 15-d in vivo study defined the acute gastrointestinal syndrome and provided an LD30/15 of 10.76 Gy, LD50/15 of 11.33 Gy, and an LD70/15 of 11.90 Gy. Intestinal crypt and villus loss were dose- and time-dependent with an apparent nadir 7 d post-irradiation and recovery noted thereafter. Severe myelosuppression and thrombocytopenia were noted in all animals, requiring the administration of antibiotics and blood transfusions. The model defines the dose response relationship and time course of acute gastrointestinal syndrome-induced morbidity and mortality in the rhesus macaque.

Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation

Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and their proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. The study data support pursuing FGF-P as a mitigator for AGS.

Multichromatic phenotypic analysis of peripheral lymphocytes in non-human primates (NHP) following total body irradiation (TBI) with 5% bone marrow shielding (BM5) (132.19)

Abstract High dose TBI of NHP leads to severe myelosuppression, neutropenia, thrombocytopenia, and immunosuppression, concurrent with an acute gastrointestinal syndrome. BM shielding mitigates these lethal effects by preserving a reservoir of unexposed hematopoietic progenitors. Rhesus macaques were exposed to either 10Gy (sub-lethal) or 11Gy (LD15 8-10 days) in the TBI/BM5 protocol and administered supportive care (fluids, antibiotics, transfusions). Peripheral blood was drawn over 150 days post irradiation (DPI) and lymphocyte subsets were assessed by flow cytometry. 10/11Gy TBI/BM5 caused a significant, early decrease in CD3+ T cells, sustained through 42 DPI, which reached baseline at 56 DPI. CD8+ T cells dominated T cell repopulation while CD4+ T cells showed a slower recovery. Most of the CD8+ T cells were CD62L+CD45RA+. CD20+ B cells reached 168% of baseline at 56 DPI and remained above baseline through 150 DPI. CD20+CD27+ memory B cell recovery kinetics were similar to B cells up to 77 DPI, with a sharp decrease at 90 DPI. CD3+ integrin α4β7+ (mucosal marker) cells recovered to 249% of baseline levels by 35 DPI and peaked at 400% of baseline at 120 DPI. Conversely, α4β7+ B cell recovery was slower, requiring 120 DPI to reach pre-irradiation levels. Functional assays will help understand the recovery pattern of lymphocyte subsets.

Scintigraphic evaluation of radiation-induced gastrointestinal motility disturbance in micro-pig model

In the previous study, we have observed that micro-pigs showed similar clinicopathological responses to human in response to high-dose radiation exposure and that there are gastrointestinal (GI) motiltity disturbances even in less amount of irradiation causing acute GI syndrome. GI motiltity disturbances is a part of radiation-induced GI syndrome and may affect infectious progression from GI tract. The specific aims of this study is to evaluate objective evidence of GI motility disturbance employing scintigraphic evaluation and to develop biomarker in evaluating radiation-induced acute GI syndrome. PWG micro-pigs (6 month-old, BW 25Kg) were locally irradiated on whole abdomen with Co60 (δ-irradiation, 5Gy, 10 Gy and 15Gy). We compared gastric emptying time and small bowel transit time using 99mTc sulfur colloid (50mCi) and gamma camera, twice before (individual control) and sequential changes after irradiation (3, 7, 10, 14, 21 days). Endoscopic evaluation and biopsy followed scintigraphic evaluation in each experiment. With whole abdominal δ-irradiation (5Gy) in micro-pigs (n=2), small bowel transit time prolonged at day 3 (2.06 and 1.97 times in each), gradually recovered and normalized at day 10. In 10Gy, 15Gy-irradiated animals (n=2), GI motility prolongation were exaggerated. Endoscopy from stomach to upper jejunum showed no definite grossly identifiable mucosal changes in 5Gy and 10Gy irradiated animals, whereas microscopic mucosal changes were evident. At 4th day after irradiation, we observed shortening of mucosal villi, dilatation of microvessels, reduced proliferating activities (Ki67 labeling index) and marked increase of apoptotic bodies (TUNEL assay) at crypts and mucosal glands. The radiation-induced mucosal changes recovered till day 22. Microscopical changes preceded clinical manifestation and grossly identifiable changes, which suggests that treatment should be started prior to symptomatic manifestation. Scintigraphic evaluation of gastric emptying and small bowel transit gave objective evidence for GI motility disturbance after radiation exposure. It could be a useful biomarker for monitering treatment effects in acute GI syndrome, which may allow validation of newly developing therapeutics for acute radiation syndrome.

Pilzvergiftungen: Toxidrome, Diagnose und Therapie

The major syndromes of mushroom poisoning can be divided by presentation timing: Early syndromes (symptom onset <6 hrs after ingestion) have little probability to cause organ damage. Epigastric pain, nausea, vomiting and diarrhea occur in most cases and treatment includes initial gastrointestinal decontamination with oral activated charcoal and fluid rehydration. In addition, an acute gastrointestinal syndrome can be combined with cholinergic toxicity, epileptiformic response or immuno-hemolytic anemia. Neurotoxic Syndromes may present as dysphoria, delirium, hallucinations or disulfiram-like reactions. Treatment is entirely supportive and if performed in hospital, the prognosis is good. Late syndromes (symptom onset >6 hrs after ingestion) are life-threatening due to liver- and renal failure. Patients who are jaundiced after an acute gastrointestinal episode, are suspected to be poisoned with Amatoxins. Patients with flank pain, hematuria, polyuria or oliguria in the absence of jaundice are suspected to have an intoxication with Cortinarius mushrooms. In both cases an intensive care management is indicated.

A set of nomograms predicting acute gastrointestinal syndrome after prostate cancer conformal radiation

15555 Background: To predict acute toxicities (tox) of the gastrointestinal syndrome (SOMA LENT) in prostate cancer (PCa) patients (pts) undergoing 3D-CRT using a tool (nomogram) with clinical as well as dosimetric variables which has proved to be significant in the AIROPROS 01–02 trial. Methods: Acute rectal tox was scored in 1,132 pts using a 10 item self assessed questionnaire (QST) describing radio-induced GI symptoms profiles for bowel frequency, tenesmus, fecal continence, rectal pain and bleeding. The correlation between hormonal therapy (HT), drug prescription, diabetes or hypertension, pelvic node or seminal vesicles irradiation, mean rectal dose, DVH constraints and rectal tox was investigated by uni- and multivariate (MVA) logistic analyses. MVA results were used the R-project software to create nomograms predicting the symptoms of the acute GI syndrome. Results: 4/10 items of the QST are reported: moderate/severe bleeding, increased bowel frequency, moderate/severe bowel urgency and severe fecal incontinence. Bleeding is related to haemorrhoids (OR=1.9), HT (protective factor, OR=0.78) and mean rectal dose (continuous variable (cv), OR=1.024). Bowel frequency is related to seminal vesicles irradiation (OR=2.8) and V60 (cv, OR=1.024), while bowel urgency is correlated to seminal vesicles irradiation (OR=3.3) and mean rectal dose (cv, OR=1.027). Fecal incontinence depends on seminal vesicles irradiation (OR=4.6) and V70 (cv, OR=1.029). MVA results were used to create a set of nomograms. Conclusions: The combined effect of several independent, prognostically valuable variables for a specific disease can be expressed using nomograms. They can evaluate clinical and technical parameters of the single pt and offer clinicians a tailored probability of a specific outcome. To our best knowledge, this work presents the first set of nomograms available in the literature specific symptoms of the GI syndrome. The prediction capability of these tools will be validated on a independent set of patients. This work was partly supported by Fondazione I. Monzino, Milan No significant financial relationships to disclose.

Reversible acute gastrointestinal syndrome associated with active systemic lupus erythematosus in patients admitted to hospital.

Patients with systemic lupus erythematosus (SLE) frequently have gastrointestinal (GI) symptoms. These are usually self-limiting and related to treatment side-effects or concurrent illness. However, abdominal pain may be due to bowel ischaemia which can lead to infarction and perforation. The likelihood of these serious events is increased in individuals with pain severe enough to require assessment in hospital or a SLEDAI score > 5. This paper describes a group of patients with active SLE and GI symptoms severe enough to require admission to hospital using a retrospective review of 52 SLE patients admitted to hospital with acute abdominal symptoms. The results showed that abdominal pain (87%), vomiting (82%) and diarrhoea (67%) had been present for a mean of 4.4 +/- 6.5 days and SLEDAI score was > or = 4 in 83% of patients. CT scanning showed evidence of serositis and bowel involvement in 63% of patients who underwent this investigation. Intravenous (iv) fluids were used in 87%, parenteral steroids in 90% and iv cyclophosphamide in 31%. Most (n = 51) were discharged well. Recurrence of GI symptoms occurred in 12 patients. The conclusions are that active SLE may manifest as an acute gastrointestinal syndrome. Early diagnosis, bowel rest, supportive medical therapy and treatment with corticosteroids and/or immunosupressives can result in a good outcome.