A retrospective study of the effects of pelvic irradiation for carcinoma of the cervix on gastrointestinal function.

PURPOSE: To evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation. METHODS AND MATERIALS: Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers. RESULTS: Stool frequency was above the control range in five patients and had increased (p < 0.001) since radiotherapy treatment. Bile acid (p < 0.001) vitamin B12 (p < 0.01) and lactose (p < 0.01) absorption were less in the patients when compared with the control subjects. Bile acid absorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p < 0.05) in those patients with lactose malabsorption. Gastric emptying (p < 0.01) and small intestinal transit (p < 0.01) were more rapid in the patients. Both small intestinal (r = -0.39, p < 0.05) and whole gut (r = -0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid absorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients. CONCLUSION: Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation.

Effect of ionizing radiation on prostaglandins and gastric secretion in rhesus monkeys.

Early radiation toxicity is characterized by nausea and vomiting. We have previously shown that gastric emptying, gastric motility, and gastric secretion were suppressed after total body exposure to irradiation. In the present studies, we evaluated the relation between vomiting and gastric function in nine rhesus monkeys and explored the possible role of prostaglandins (PG) in these phenomena. The concentration of PG in plasma and gastric juice was determined using a standard radioimmunoassay and gastric acid output was measured concurrently using a marker dilution technique. The animals were studied in the basal state and after total body exposure to 800 cGy 60Co delivered at a rate of 500 cGy/min. Acid output was abolished from 40 min to 2 h after irradiation but had returned to preirradiation levels 2 days later. Plasma PGE2 and PGI2 (as measured by 6-keto-PGF1 alpha determination) were not significantly modified by irradiation. In contrast, irradiation produced an immediate significant increase (P less than 0.05) in gastric juice concentration of PGE2 (318 +/- 80 to 523 +/- 94 pg/ml; mean +/- SE) and PGI2 (230 +/- 36 to 346 +/- 57 pg/ml); both had returned to basal levels 2 days later. Thus, an increase in gastric juice concentration of both PGE2 and PGI2 is associated with the radiation induced suppression of acid output.

A model for treating post-irradiation nausea and vomiting in man: the action of insulin in abolishing radiation-induced delay in gastric emptying in the rat.

Radiation-induced delay in gastric emptying in rats, which may be comparable to radiation-induced nausea and vomiting in man, can be successfully treated with insulin. Biphasic insulin, given in the appropriate dose for the radiation exposure, restored the rate of emptying to normal and was used instead of soluble insulin which made the stomach empty quicker than normal. Some of the evidence suggests that this effect of insulin is related to its action on carbohydrate metabolism, but there was no simple correlation between the hypoglycaemic action of insulin and its effect on stomach emptying. A complete explanation for this action of insulin cannot be given at this stage but the possible involvement of intestinal hormones, such as enteroglucagon is discussed. It is suggested that the use of insulin to treat radiation-induced nausea and vomiting in man should be considered.

Does local irradiation affect gastric emptying in humans?

The authors measured gastric emptying in 13 patients undergoing radiation therapy to the chest, abdomen, or pelvis for nongastrointestinal cancer to investigate whether gastric emptying (GE) was altered by this therapy. Symptoms and weight were monitored at regular intervals. Patients served as their own controls and were compared to a group of healthy subjects. When studied prior to radiation therapy (baseline), cancer patients had a gastric emptying rate that was similar to a healthy control group (t1/2 mean+/-SEM 92.0+/-15.3 vs. 80.4+/-8.2 min). Irradiation did not change the emptying rate, either after the first dose (early) of 180 cGy (t1/2 99.5+/-17.9) or after 2 weeks of therapy (late) with 3000 cGy (t1/2 75.5+/-7.3). There was no correlation of radiation field or tumor type with gastric emptying rate. Two of the 13 patients experienced nausea and vomiting during their course of radiation, but their gastric emptying was unchanged from baseline.

Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor.

Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 microg/rat, icv) decreased 2-3 h and 3-6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 microg/rat) had no effect. The corticotropin-releasing factor (CRF)(1)/CRF(2) antagonist astressin-B or the CRF(2) antagonist astressin(2)-B abolished icv nesfatin-1's anorexigenic action, whereas an astressin(2)-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin(2)-B. Nesfatin-1 into the 4v (0.05 microg/rat) or ic (0.5 microg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin(2)-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF(2)-receptor-dependent pathways after forebrain injection and CRF(2)-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.

Gammagrafía de tránsito gastrointestinal en el estudio del estreñimiento crónico en edad pediátrica; una exploración infrecuente / Gastrointestinal transit scintigraphy in chronic constipation evaluation in pediatric age; an infrequent test

Objetivo. El estreñimiento crónico es una enfermedad común en el niño. Nuestro objetivo fue poner de manifiesto la utilidad de la gammagrafía de tránsito gastrointestinal en el estudio de pacientes pediátricos con estreñimiento crónico y las ventajas que tiene respecto a otros estudios de imagen, a pesar de nuestra limitada experiencia. Material y métodos. Se valoraron 5 pacientes remitidos a nuestro servicio con diagnóstico de estreñimiento crónico refractario al tratamiento. Se realizó un protocolo de estudio completo, incluyendo gammagrafía de vaciamiento gástrico para líquidos y tránsito de intestino delgado y grueso, utilizándose una única dosis de 111In-DTPA. Siguiendo guías internacionales se definieron áreas de interés en estómago, íleon terminal y en 6 regiones del intestino grueso. Resultados. Todos los enfermos presentaron estudios gammagráficos alterados, mostrando 4 de ellos exploraciones radiológicas normales. El estudio radioisotópico cambió el diagnóstico del paciente en 2 casos y en otros 2 contribuyó a aclararlo, ante la discordancia entre pruebas radiológicas normales y biopsia rectal patológica. Uno de los pacientes mostró concordancia entre los 2 estudios de imagen. Tras la gammagrafía se produjo cambio en el manejo terapéutico en 2 casos. Conclusiones. Nuestra limitada experiencia coincide con los datos publicados en los que el estudio gammagráfico resulta ser un método reproducible y preciso. Proporciona una información fisiológica, cuantitativa y útil en el estudio del estreñimiento, siendo la única exploración que permite la determinación tanto global como regional del tiempo de tránsito gastrointestinal (AU)

Aim. Chronic constipation is a common pathology in children. The aim of this paper was to show the usefulness of gastrointestinal transit scintigraphy in pediatric patients with chronic constipation, and the advantages with respect to other imaging techniques, despite our limited experience. Material and methods. We evaluated 5 patients sent to our service with a diagnosis of chronic constipation refractory to treatment. We performed a complete study protocol, including liquid gastric emptying scintigraphy and small and large bowel transit times, using a single dose of 111In-DTPA. Following international guidelines regions of interest were defined in stomach, terminal ileum and in 6 regions of the large intestine. Results. All patients showed altered scintigraphy study, showing 4 of them normal radiological tests. Radioisotopic study changed diagnosis in 2 patients and in other 2 patients contributed to clarify it, since discordance between normal radiological tests and abnormal rectal biopsy. One of the patients showed concordance between each imaging modality. The results of the test changed the therapeutic management in 2 cases. Conclusions. Our limited experience coincides with published data in which scintigraphy study turns out to be a reproducible and accurate method. It provides physiological, quantitative and useful information in the study of constipation, being the unique exploration that allows both global and regional gastrointestinal transit time determination (AU)

Effect of feed temperature and phototherapy on gastric emptying in the neonate.

The effect of feed temperaturae and phototherapy on the rate of stomach emptying was studied in healthy infants during the first week. Emptying rate was measured by the modified serial test meal technique using 10% Dextrose feeds. The results show that emptying rate is independent of feed temperature and is not affected by phototherapy.

[The role of the autonomic nervous system in regulating the excretory function of the stomach in irradiated dogs]. / Rol' vegetativnoi nervnoi sistemy v reguliatsii ékskretornoi funktsii zheludka obluchennykh sobak.

Dogs and rats were exposed to gamma/neutron- and X-radiation. The anterior part of dog's stomach was exposed to 10 Gy and 13 Gy respectively; rats were subjected to whole-body irradiation with absolutely lethal doses. Prior to irradiation, various parts of the vegetative nervous system of both types of animals were "switched off" pharmacologically. In addition to clinical investigation of radiation sickness, the excretory function of the stomach was studied by the excretion of intravenously injected neutral red. The "switching-off" of the parasympathetic nervous system prior to irradiation stabilized the excretory processes in the stomach, increased the resistance of animals, and, vice versa, the "switching-off" of the sympathetic nervous system destabilized the excretory processes and decreased the resistance of the organism.

[Gastric excretory function in dogs and its role in radiation lesions]. / Ekskretornaia funktsiia zheludka sobak i ee rol' v usloviiakh luchevogo porazheniia.

X-irradiation was shown to cause a 2-3-fold increase in the excretion of intravenously administered 1% neutral red and endogenous ammonia. It is suggested that elimination of excreta from the stomach may change the course of radiation sickness. The postirradiation gastric lavage alleviates the clinical picture of the disease, increases the survival rate and protects the gastric mucosa from "poisoning".

[The use of low-intensity laser irradiation in the immediate postoperative period in patients with gastroduodenal ulcer]. / Primenenie nizkointensivnogo lazernogo izlucheniia v blizhaishem posleoperatsionnom periode u bol'nykh s gastroduodenal'noi iazvoi.

In patients with an ulcer of the stomach and duodenum at the immediate postoperative period in the complex of treatment, the low intensity laser irradiation of the anastomosis (after gastric resection) and ulcer (after the organ-preserving operations) according to the developed method by means of the modified LG-75 apparatus was used. The use of a helium-neon laser contributed to development of the severe form of anastomositis and subsequent gastrostasis. In study of gastric secretion, no considerable changes in acid formation were revealed.

Altered gastric emptying and prevention of radiation-induced vomiting in dogs.

The relation between radiation-induced vomiting and gastric emptying is unclear and the treatment of this condition is not established. We explored, therefore, (a) the effect of cobalt 60 irradiation on gastric emptying of solids and liquids and (b) the possibility of preventing radiation-induced vomiting with the dopamine antagonist, domperidone. Twenty dogs were studied on two separate days, blindly and in random order, after i.v. injection of either a placebo or 0.06 mg/kg domperidone. On a third day, they received 8 Gy (800 rads) whole body irradiation with cobalt 60 gamma-rays after either placebo (n = 10) or domperidone (n = 10). Before each study, each dog was fed chicken liver tagged in vivo with 99mTc-sulfur colloid (solid marker), and water containing 111In-diethylenetriamine pentaacetic acid (liquid marker). Dogs were placed in a Pavlov stand for the subsequent 3 h and radionuclide imaging was performed at 10-min intervals. Irradiation produced vomiting in 9 of 10 dogs given placebo but only in 1 of 10 dogs pretreated with domperidone (p less than 0.01). Gastric emptying of liquids and solids was significantly suppressed by irradiation (p less than 0.01) after both placebo and domperidone. These results demonstrate that radiation-induced vomiting is accompanied by suppression of gastric emptying. Furthermore, domperidone prevents vomiting produced by ionizing radiation but does not alter the accompanying delay of gastric emptying.

[Recurrent gastroparesis following abdominal irradiation. Therapy with cisapride]. / Rezidivierende Gastroparese nach Abdomenbestrahlung. Therapie mit Cisaprid.

Following abdominal radiation a 16-year-old male patient developed nausea and vomiting secondary to gastric stasis, dilatation and impairment of antral motility. Symptoms improved after 2 months of treatment with a cholinergic agonist. Now, 7 years later, symptoms recurred. Cisapride, a newly developed agent which stimulates gastrointestinal motility probably evoked a prompt increase of antral motility and gastric emptying. We conclude that abdominal irradiation may cause gastrointestinal motility disturbances which may respond to medical therapy.

Effect of ionizing radiation on gastric secretion and gastric motility in monkeys.

The prodromal syndrome of radiation sickness is characterized by nausea and vomiting but the pathophysiology and the treatment of this entity is largely unknown. We investigated this problem by determining the effects of ionizing radiation on gastric function with and without administration of the dopamine antagonist domperidone. We measured gastric electrical control activity (waves per minute), fractional emptying rate (percent per minute), acid output (microequivalents per minute), and plasma levels of immunoreactive beta-endorphin. Twelve conscious, chair-adapted rhesus monkeys were studied twice before, once immediately after, and once 2 days after a single 800-cGy (800 rads) 60Co total body irradiation. In addition to causing vomiting, total body irradiation transiently suppressed gastric electrical control activity, gastric emptying and gastric secretion, while increasing plasma levels of immunoreactive beta-endorphin. Domperidone had no effect on vomiting or gastric function either before or after irradiation, but it significantly increased plasma immunoreactive beta-endorphin.

[Acute and chronic disorders in gastric emptying after the x-ray irradiation of the rat stomach and their therapeutic modification]. / Akute und chronische Störungen in der Magenentleerung nach Röntgenbestrahlung des Rattenmagens und deren therapeutische Beeinflussbarkeit.

After localized 300 kV X-irradiation of the rat stomach the stomach emptying time of a liquid and a solid test meal was examined with a non-invasive radiological method. In the acute period one to three weeks after irradiation with single doses between 10.7 and 21.3 Gy we observed a faster emptying of the liquid and a delayed emptying of the solid test meal. The faster emptying of the liquid test meal was treated successfully with atropine. In the chronic period we observed a delayed emptying of the liquid and of the solid test meal. These emptying disorders were treated partially successfully with the parasympathomimeticum carbachol and they were treated completely successfully with the dopamine antagonist metoclopramide.

Esvaziamento gástrico com tecnécio após ressecção ou exclusão jejunoileal extensa: estudo em ratos / Gastric empyting after extensive intestinal resection: study in rats

Racional - Existem diferentes opiniões a cerca do esvaziamento gástrico após extensas ressecções intestinais. Objetivos - Determinar a existência de um retardo no esvaziamento gástrico após ressecção ou exclusão jejunoileal extensa. Materail e Método - Oitenta e um ratos Wistar foram operados e os animais foram divididos em três grupos, sendo o primeiro submetido a laparotomia seguida de secção do jejuno e anastomose término-terminal, sem ressecção; o segundo grupo submetido a ressecção de todo o intestino situado entre os 10 cm proximais do jejuno e os 10 cm distais do íleo, com anastomose jejuno-ileal término-terminal; e o último grupo teve o segmento de intestino delgado, com as características do grupo anterior, derivado para o cólon. Trinta dias após os procedimentos operatórios, os animais receberam, por gavagem, uma dieta pastosa contendo resina marcada com tecnécio. Cada grupo foi, então, dividido em três subgrupos, relaparotomizados 15, 60 e 120 minutos após a infusão da dieta marcada. O tubo digestivo foi dividido por ligaduras em três segmentos: estômago, intestino delgado e intestino grosso. Em cada segmento, a radioatividade foi medida em gamacâmara. Resultados - Há um retardo no esvaziamento gástrico após ressecção e exclusão jejunoileal extensa, mais acentuado no grupo que sofreu exclusão. Conclusão - Apesar do retardo no esvaziamento gástrico, o cólon dos animais que sofreram ressecção ou exclusão jejunoileal extensa apresentava maior retenção de radioisótopos que o grupo controle.