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Thread: Post-irradiation Colitis Pictures - Atlas of Colon and Ileum

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    Default Post-irradiation Colitis Pictures - Atlas of Colon and Ileum

    INTRODUCTION
    Radiation colitis is an insidious, progressive disease of increasing frequency. It is usually iatrogenic and unavoidable and frequently develops 6 mo to 5 years after regional radiotherapy for malignancy. About half of all patients with malignancies undergo irradiation as part of their therapy. Considerable morbidity and mortality accompany radiation treatment because of the deleterious effects on adjacent normal tissues, mainly the colon and the small intestine. The type and extent of injury, depending on the dose of the radiation and the radiation sensitivity of the gut and the duration, is highly variable, ranging from 3 mo to 30 year. Serious consequences may develop after years of gestation, and the disease, its treatment, and the disability produced are formidable. Apart from acute radiation colitis, manifestations of chronic radiation injury include proctitis, hemorrhages, fistulas, abscesses with signs of sepsis, perforations, strictures, and even cancer. Therefore, novel means to increase resistance of the intestine to radiation damage and effective therapeutic strategies are needed to prevent and manage this disease.

    MANAGEMENT OF COLITIS CAUSED BY IRRADIATION
    In general, prior to start, each treatment should be individualized, and any predisposing factor should be identified during its course in order to early recognize and treat complications. Once complications have arisen, it is best to deal with the irradiated tissue by the most conservative modality, because the areas of intestinal injury do not tend to heal. This may require early diversion or resection as conservative therapy, because fistulas and bleeding will become recurrent and intractable. The effectiveness of non-surgical approaches remains far from desirable, and bleeding recurrence represents a major drawback that leads to a need for consecutive therapeutic sessions and combination of techniques If diversion fails to control bleeding, resection is necessary, even if it involves an abdominoperineal resection.

    From another general viewpoint, there is a similarity in the activation of mucosal cytokines between inflammatory bowel disease (IBD) and radiation proctosigmoiditis. Indeed, as in the case of IBD patients, the mucosal levels of interleukin (IL)-2, -6, and -8 are significantly higher in both diseased and normal segments of colon in patients with radiation proctitis, compared with normal controls. In addition, IL-1β levels are significantly higher in diseased segments, compared with endoscopically normal-appearing segments in radiation proctitis. Tumor necrosis factor-alpha (TNF-α) levels are also significantly elevated in irradiated mice compared with non-irradiated controls. These data may partially explain the beneficial effects of similar systemic and topical drugs including mesalamine compounds and steroids when used in radiation-induced proctosigmoiditis
    Post-irradiation Colitis Pictures Atlas Colon attachment.php?s=a298a13ad8800e13a50e5a63b4071534&attachmentid=2728&d=1443376740

    Empirical-experimental management
    The majority of acute radiation colitis is self-limited, and only supportive management is required[7]. It must be emphasized, however, that acute radiation syndrome with a threshold dose of 8 Gy in man, represents a lethal clinical-pathological unit, enteritis and proctocolitis necro-hemorrhagica, with unknown causal therapy. In this respect, the detection of phospho-Elk-1, a protein acting as a transcription factor activating specific genes, might be considered as a suitable and very sensitive marker of acute radiation-induced injury of large and small intestine. Whether Elk-1 inhibitors, such as the compound A (CpdA) or the protective agent U0126 diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)-butadiene], the effect of which probably results from the IL-1β mRNA reduction via the inhibition of ERK pathway, can be used in the management of this syndrome remains to be investigated.

    Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The migration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. Specifically, circulating leukocytes are recruited to sites of inflammation by a well-regulated and coordinated process that largely occurs in postcapillary venules. Adhesion molecules are expressed on the surface of endothelial cells, and leukocytes are involved in an orderly sequence of cell-cell interactions that include leukocyte adherence to vascular endothelium and the subsequent transendothelial migration into the inflamed tissue. Finally, reactive oxygen metabolites produced by activated leukocytes can induce damage to various cellular components, including structural and regulatory proteins, carbohydrates, lipids, DNA and RNA. In this respect, upregulation of intercellular adhesion molecule (ICAM)-1 and the accumulation of inflammatory myeloperoxidase-positive cells have been observed during acute radiation colitis prior to an overt radiation-induced ulcer, thereby playing important roles in the development of radiation-induced colonic ulcer Moreover, there is direct in vivo evidence that antioxidant mechanisms of the intestinal mucosa are not mobilized during the acute tissue radiation response; four days after exposure, during the inflammatory phase, superoxide dismutases (SOD) and catalase are decreased and glutathione peroxidases and metallothioneins are induced. Dexamethasone treatment modulates only glutathione peroxidase expression and does not influence either metallothionein or SOD expression. These experimental data indicate that during the radiation-induced acute inflammatory response, an imbalance of the antioxidant network of intestinal mucosa occurs.

    In view of the aforementioned data, modulation of the leukocyte recruitment and activation pathway seems to be a potential therapeutic strategy against acute radiation colitis. Further supporting this consideration, experimental studies have demonstrated that leukocyte rolling is mediated by P-selectin and that firm leukocyte adhesion is supported by lymphocyte function antigen-1 in radiation-induced colitis. P-selectin-dependent leukocyte rolling is a precondition for subsequent leukocyte adhesion in radiation-induced intestinal damage. Therefore, targeting P-selectin and/or lymphocyte function antigen-1 might protect against pathologic inflammation in the colon induced by radiotherapy[13]. Moreover, Cu/Zn-SOD1 supplementation in an experimental model of radiation-induced intestinal inflammation has also been shown to decrease oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. Specifically, a significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules is observed after irradiation. Although administration of SOD1 has no effect on leukocyte rolling, it decreases leukocyte adhesion to intestinal venules significantly and in a dose-dependent way. Treatment with SOD1, at doses that reduce leukocyte recruitment, abrogates the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, is also significantly reduced by SOD1.
    Post-irradiation Colitis Pictures Atlas Colon attachment.php?s=a298a13ad8800e13a50e5a63b4071534&attachmentid=2729&d=1443376751

    Diarrhea associated with acute radiation colitis frequently resolves with anti-diarrheal medications and by reducing fat and lactose intake. The diarrhea rarely requires discontinuation of treatment unless chemotherapy is given concurrently with radiation. Intractable diarrhea during the combined treatment may require hospital admission for administration of parenteral feeding. Elementary diet may also be introduced as an alternative to parenteral nutrition

    Patients refractory to anti-diarrheal medications may benefit from administration of the synthetic somatostatin analog octreotide. Specifically, it has been shown that subcutaneous octreotide administration (150 μg t.i.d.) for 5 d is apparently an effective, well-tolerated treatment modality for concurrent chemoradiotherapy-induced diarrhea refractory to loperamide Octreotide appears to be more effective than conventional therapy with diphenoxylate and atropine in controlling acute radiation-induced diarrhea and eliminating the need for radiotherapy interruptions

    Apart from anti-diarrheal medications, other measures of general management of acute radiation enteropathy include administration of antiemetics. Steroid-containing suppositories may be helpful in the treatment of patients with anorectal inflammation. Severe neutropenia from chemotherapy might require growth factors, such as recombinant granulocyte colony-stimulating factor (G-CSF, filgrastim) or granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) to shorten the period of neutropenia, and avoid excessively delayed therapy from the bone marrow depression. G-CSF is a cytokine known to activate neutrophils in vivo and GM-CSF mediates its effects on the neutrophil lineage through its effects on phagocytic accessory cells and its synergy with G-CSF.

    Epidermal growth factor, an endogenous peptide, trophic to the gastrointestinal tract, significantly decreases the acute clinical manifestations of experimental radiation enteritis Therefore, it may be effective in human acute radiation colitis

    Empirical-experimental management
    Chronic radiation colitis is recognized as a frequent and clinically important sequel of abdominal and pelvic irradiation treatment for malignant disease. Since radiotherapy is now being used more than ever before in the therapy of solid organ neoplasms of the abdomen and the pelvis, the incidence of radiation colitis is likely to increase in the futureImportantly, it is a precancerous lesion: Radiation-associated rectal cancer originates from dysplasia due to radiation colitis and has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis. Therefore, management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease that includes development of fibrosis, endarteritis, edema, fragility, perforation, partial obstruction, and even cancer. Patients with this condition are commonly managed conservatively. Because the obstruction is only partial, decompression is easily achieved by nasogastric suction and parenteral support. The patient is then often discharged on a liquid-to-soft diet. However, this therapeutic regimen does nothing for the underlying pathology. Although total parenteral nutrition corrects denutrition and facilitates deferred surgery in some patients, severe radiation enteritis remains a poorly predictable progressive disease with numerous relapses. The problem, sooner or later, will return with the patient further depleted by the chronic radiation colitis. In a recent meta-analysis assessing the incidence and significance of malnutrition and examining the efficacy of therapeutic nutritional interventions used to manage
    Post-irradiation Colitis Pictures Atlas Colon attachment.php?s=a298a13ad8800e13a50e5a63b4071534&attachmentid=2730&d=1443376765

    gastrointestinal side effects in patients undergoing pelvic radiotherapy, it has been shown that there is no evidence favoring the use of nutritional interventions to prevent or manage bowel symptoms attributable to radiotherapy. Regarding the underlying pathology, vascular damage consisting of fibrin thrombi, fibrinoid necrosis and subintimal thickening of the arterioles leads to persistent local ischemia, which results in diffuse fibrosis of the lamina propria and submucosa. The diffuse fibrosis, in turn, accelerates vascular damage and further worsens local ischemia, forming a vicious cycle, finally leading to ulceration of the bowel wall and serious complications including massive gastrointestinal hemorrhages and perforations Therefore, surgical intervention appears to be appropriate when the diagnosis of chronic radiation colitis is confirmed

    References:
    Recent advances in the management of radiation colitis











    Last edited by Medical Photos; 09-27-2015 at 05:59 PM.

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