Optogenetic Induction of Colonic Motility in Mice.

BACKGROUND & AIMS: Strategies are needed to increase gastrointestinal transit without systemic pharmacologic agents. We investigated whether optogenetics, focal application of light to control enteric nervous system excitability, could be used to evoke propagating contractions and increase colonic transit in mice. METHODS: We generated transgenic mice with Cre-mediated expression of light-sensitive channelrhodopsin-2 (ChR2) in calretinin neurons (CAL-ChR2 Cre+ mice); Cre- littermates served as controls. Colonic myenteric neurons were analyzed by immunohistochemistry, patch-clamp, and calcium imaging studies. Motility was assessed by mechanical, electrophysiological, and video recording in vitro and by fecal output in vivo. RESULTS: In isolated colons, focal light stimulation of calretinin enteric neurons evoked classic polarized motor reflexes (50/58 stimulations), followed by premature anterograde propagating contractions (39/58 stimulations). Light stimulation could evoke motility from sites along the entire colon. These effects were prevented by neural blockade with tetrodotoxin (n = 2), and did not occur in control mice (n = 5). Light stimulation of proximal colon increased the proportion of natural fecal pellets expelled over 15 minutes in vitro (75% ± 17% vs 32% ± 8% for controls) (P < .05). In vivo, activation of wireless light-emitting diodes implanted onto the colon wall significantly increased hourly fecal pellet output in conscious, freely moving mice (4.2 ± 0.4 vs 1.3 ± 0.3 in controls) (P < .001). CONCLUSIONS: In studies of mice, we found that focal activation of a subset of enteric neurons can increase motility of the entire colon in vitro, and fecal output in vivo. Optogenetic control of enteric neurons might therefore be used to modify gut motility.

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)

Coloduodenal and enterocutaneous fistula in twins with Crohn’s disease

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Light-emitting diodes at 940nm attenuate colitis-induced inflammatory process in mice.

Inflammatory bowel disease (IBD) presents intense inflammatory infiltrate, crypt abscesses, ulceration and even loss of function. Despite the clinical relevance of IBD, its current therapy remains poorly effective. Infrared wavelength phototherapy shows therapeutic potential on inflammation. Our goal was to evaluate whether light-emitting diodes (LED) at 940nm are capable of mitigating the colitis-induced inflammatory process in mice. Forty male Swiss mice were assigned into five groups: control; control treated with LED therapy; colitis without treatment; colitis treated with LED therapy; colitis treated with Prednisolone. Experimental colitis was induced by acetic acid 7.5% (pH2.5) rectal administration. LED therapy was performed with light characterized by wavelength of 940nm, 45nm bandwidth, intensity of 4.05J/cm(2), total power of 270mW and total dose of 64.8J for 4min in a single application. Colitis-induced intestinal transit delay was inhibited by LED therapy. Colitis caused an increase of colon dimensions (length, diameter, total area) and colon weight (edema), which were inhibited by LED therapy. LED therapy also decreased colitis-induced tissue gross lesion, myeloperoxidase activity, microscopic tissue damage score and the presence of inflammatory infiltrate in all intestinal layers. Furthermore, LED therapy inhibited colitis-induced IL-1ß, TNF-α, and IL-6 production. We conclude LED therapy at 940nm inhibited experimental colitis-induced colon inflammation in mice, therefore, rendering it a promising therapeutic approach that deserves further investigation.

Neumonía por aspiración diagnosticada mediante gammagrafía SPECT/TAC de tránsito esofágico / Aspiration pneumonia diagnosed by esophageal transit SPECT/CT scintigraphy

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Tetania y convulsiones, síntomas de debut de la enfermedad de Crohn / Tetany and convulsions: onset symptoms in Crohn’s disease

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Pathophysiology of late anorectal dysfunction following external beam radiotherapy for prostate cancer.

BACKGROUND: Patients treated with external beam radiotherapy (EBRT) may suffer from long-term anorectal adverse effects. The purpose of the present study was to assess long-term functional and structural anorectal changes in patients previously treated with EBRT for prostate cancer and to suggest the mechanism behind the development of the adverse effects. MATERIAL AND METHODS: Our previously proposed RT-induced anorectal dysfunction (RT-ARD) score, developed with the intention to survey anorectal dysfunction was used to identify patients with and without anorectal symptoms. Among 309 patients surveyed with the questionnaire, we chose 23 patients with the highest RT-ARD score and 19 patients with the lowest RT-ARD score. They were investigated by multimodal rectal sensory stimulation, standard anal physiological tests. Changes of the rectal mucosa were assessed by flexible sigmoidoscopy and graded by the Vienna Rectoscopy Score (VRS). RESULTS: The mean follow-up time was 3.8 (range, 2.8; 8.6) years in patients with high RT-ARD and 3.8 (range, 2.6; 5.9) in patients with low RT-ARD. Endoscopic evaluation revealed higher VRS scores in patients with high RT-ARD compared to patients with low RT-ARD (p = 0.002). Patients with high RT-ARD had increased rectal sensory response to distension manifested both as volume (p = 0.006) and cross-sectional area (p = 0.04), and they had reduced maximum anal resting pressure assessed by anal manometri (p = 0.02). CONCLUSIONS: Long-term anorectal symptoms correlate to changes in anorectal biomechanical properties and rectal mucosal injury. Our data suggests that RT-induced long-term anorectal dysfunction is multifactorial caused by injury of the rectal mucosa and the internal anal sphincter combined with increased rectal sensitivity and reduced rectal functional capacity.

Radiación ionizante en pacientes con enfermedad de Crohn. Estimación y factores asociados / Ionizing radiation in patients with Crohn's disease. Estimation and associated factors

Introducción: la exposición a radiación ionizante se asocia a un mayor riesgo de desarrollar tumores. Los pacientes con enfermedad de Crohn requieren habitualmente múltiples pruebas de imagen que utilizan este tipo de radiación. Objetivos: los objetivos de este estudio son estimar la dosis total de radiación ionizante recibida por pacientes con enfermedad de Crohn a lo largo de su evolución e identificar los factores asociados a dosis de radiación más altas. Métodos: se incluyeron 235 pacientes con enfermedad de Crohn diagnosticados entre 1972 y 2010. Se calculó retrospectivamente la dosis efectiva (DE) recibida por cada paciente, teniendo en cuenta los tránsitos gastrointestinales y las tomografías computarizadas que se habían realizado. Basados en estudios epidemiológicos previos, se consideró un valor umbral de DE ≥ 50 mSv de mayor riesgo de desarrollar cáncer. Resultados: la media de DE recibida por paciente fue 33,4 mSv (IC 95% 29,3-37,5). Un total de 49 (20,8%) pacientes recibió una DE >= 50 mSv. Se identificaron como factores predictivos independientes asociados a una DE >= 50 mSv: edad mayor de 40 años, necesidad de cirugía, edad al diagnóstico menor 16 años y tiempo de evolución mayor de 8 años. Conclusiones: un porcentaje considerable de pacientes con enfermedad de Crohn recibe dosis elevadas de radiación ionizante potencialmente carcinogénicas. La identificación de los pacientes mas susceptibles a recibir dosis altas de radiación, la monitorización de la dosis efectiva recibida y la utilización de pruebas de imagen que no utilizan radiación ionizante (enterorresonancia, ecografía abdominal), podrían contribuir a reducir la exposición a la radiaciones ionizantes potencialmente carcinogénicas(AU)

Introduction: exposure to ionizing radiation is associated with an increased risk of developing tumors. Patients with Crohn’s disease (CD) usually require multiple imaging tests using this type of radiation. Objectives: the objectives of this study were to estimate the total dose of ionizing radiation received by patients with Crohn’s disease during their course and to identify the factors associated with higher radiation doses. Methods: two hundred thirty-five CD patients diagnosed between 1972 and 2010 were included. The effective dose (ED) received by each patient was calculated retrospectively based on the number of gastrointestinal transit studies and computed tomography scans performed. Considering recent epidemiological studies, an ED greater than or equal to 50 mSv was used as the cut-off point for increased risk of developing cancer. Results: the mean ED received per patient was 33.4 mSv (95% CI 29.3-37.5). A total of 49 (20.8%) patients received an ED >= 50 mSv. The following factors were identified as independent predictors associated with an ED >= 50 mSv: Age older than 40 years, need for surgery, age under 16 years at diagnosis and disease duration over 8 years. Conclusions: a substantial proportion of patients with Crohn’s disease receive high doses of potentially carcinogenic ionizing radiation. Identification of the most susceptible patients to receive high doses of radiation, monitoring of effective doses received and the use of imaging techniques that do not require ionizing radiation (MR enterography, abdominal ultrasound) could contribute in reducing patients’ exposure to potentially carcinogenic ionizing radiation(AU)

Splitting the scotoperiod: effects on feeding behaviour, intestinal fill and digestive transit time in broiler chickens.

1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light schedule with two equally spaced 4-h scotoperiods (DARK 4 + 4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each of 64 birds. Empty intestinal weights as well as their contents were measured weekly at 4 time points (n = 192). Digestive transit time was estimated on d 29 using a chromic oxide marker; production variables and the extent of foot pad dermatitis were also recorded. 4. In the 3 h prior to a scotoperiod, feeding activity increased in chickens from DARK 8 but not DARK 4 + 4. This increase was reflected in a higher relative content of the crop in DARK 8 at this time. 5. Immediately following the scotoperiod, feeding activity peaked and, although the chickens in DARK 4 + 4 expressed more feeding behaviour in the first 20 min after the scotoperiod, the chickens in DARK 8 had overall higher feeding activity across the day. However, DARK 4 + 4 had a higher feed intake and weight gain. The occurrence and severity of foot pad dermatitis was similar between treatments. 6. In conclusion, broilers modify their feeding behaviour according to the prevailing light schedule. Eight consecutive hours of darkness reduced growth, but did not affect overall feed conversion efficiency, and did not appear to exacerbate hunger or foot pad dermatitis to any great extent.

Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate.

PURPOSE: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. PATIENTS AND METHODS: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. RESULTS: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. CONCLUSION: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.

Neuromuscular electrical stimulation of completely paralyzed abdominal muscles in spinal cord-injured patients: a pilot study.

STUDY DESIGN: Prospective placebo-controlled. OBJECTIVE: The effect of abdominal neuromuscular electrical stimulation (NMES) in patients with spinal cord injury. The principal parameters observed in this study are lung capacity, colonic transit, patient satisfaction of used method and of aesthetics effect on abdominal wall. SETTINGS: Centre de Traumatologie et de Réadaptation, Brussels, Belgium. METHODS: A total of 10 volunteers participated in this study and were assigned to two groups-the effective electrical stimulation group (ESG) and the placebo-controlled group (PG). NMES of abdominal muscles was performed 25 min per day for 8 weeks. RESULTS: NMES significantly decreased forced vital capacity (FVC) in ESG but not in PG. In ESG, colonic transit was accelerated in ascending, transverse and descending colon but transit in rectosigmoideum was not affected. In PG, no variations in colonic transit were observed. Satisfaction scale shows a better influence on aesthetics effect in ESG than in PG. CONCLUSION: This pilot study shows that NMES of paralyzed abdominal muscles positively affects colonic transit except in rectosigmoideum segment and negatively affects FVC. It could be a simple self-used method to regulate colonic transfer with considerably good cosmetic effect on abdominal wall. However, regular verification of FVC will probably be necessary.

Effects of radiation therapy on oesophageal transit in patients with inner quadrant breast tumour.

OBJECTIVES: The aim of this study was to evaluate quantitatively the effect of low doses of radiation therapy on the oesophageal transit in patients with inner quadrant breast carcinoma. METHODS: Eighteen female patients with locally advanced inner quadrant breast tumour were included in this study. A total dose of 5000 cGy in 25 fractions of 200 cGy was applied from four different treatment portals to all patients. Oesophageal motility was evaluated before and immediately after radiotherapy using oesophageal scintigraphy. The oesophageal transit times (ETTs) for the upper one-third, the lower two-thirds portion and the whole oesophagus were calculated. RESULTS: The upper one-third portion of the oesophagus received a mean dose of 600 cGy and the lower two-thirds portion received a mean dose of 1530 cGy as a result of 5000 cGy dose application. All of the patients developed grade 1 oesophageal toxicity. Post-radiation therapy ETT values were significantly higher compared to pre-radiation therapy ETT values (P<0.001). Before irradiation, ETT values for the upper one-third, distal two-thirds of the oesophagus and the whole oesophagus were 4.77+/-1.08, 11.22+/-2.85 and 11.61+/-2.97 s, respectively. After irradiation, ETT values for the upper one-third, distal two-thirds of the oesophagus and the whole oesophagus were 6.92+/-2.15, 23.30+/-5.65 and 23.74+/-5.70 s, respectively. CONCLUSIONS: Oesophageal transit seems to be affected by radiation even without a clinically significant oesophageal symptom and oesophageal scintigraphy allows sensitive, non-invasive and quantifiable assessment of the oesophageal transit time.

Single millimeter wave treatment does not impair gastrointestinal transit in mice.

Millimeter wave treatment (MWT) is based on those biological effects that develop following skin exposure to low power electromagnetic waves. This method of treatment is in wide clinical use in several Eastern European countries for treatment of a variety of conditions, including pain syndromes. However, most treatment modes of MWT were developed empirically, and certain indications and contraindications for the use of MWT remain to be established. In our previous blind experiments we have shown that the hypoalgesic effect of MWT may be quantitatively evaluated, and most probably mediated by the neural system in general, and the system of endogenous opioids in particular. Taking in consideration a well-known ability of opioids to cause gastrointestinal disturbances, which could limit clinical application of MWT, the main aim of the present study was to investigate whether a single MWT, that can produce opioid-related hypoalgesia, may also retard gut transit and colorectal passage in mice. The charcoal meal test was used to quantitatively evaluate upper gastrointestinal transit, and the glass bead test was employed to examine colonic propulsion in mice. MWT was applied to the nose area of mice. The MWT characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm(2); and duration = 15 min. The results obtained have shown that MWT does not significantly change small intestinal or colonic transit in mice, and thus suppression of gastrointestinal motility should not be a setback in the clinical use of MWT.

The effects of abdominal irradiation for seminoma of the testis on gastrointestinal function.

To evaluate the long-term effects of abdominal irradiation for the treatment of seminoma of the testis on gastrointestinal function, 15 randomly selected patients who had been treated for stage I seminoma of the testis 2-10 years previously had the following parameters of gastrointestinal function evaluated: gastrointestinal symptoms; absorption of bile acid; vitamin B12; lactose and fat; gastric emptying; small intestinal and total gut transit; and intestinal permeability. Results were compared to those obtained in 18 normal volunteers. There was an increased prevalence of gastrointestinal symptoms (P < 0.01) in the patients and stool frequency was above the control range in two of them. Gastric emptying was faster (P < 0.01) in the patients. There were no significant differences in vitamin B12, bile acid, lactose or fat absorption, small intestinal transit or whole gut transit between the two groups, although faecal fat excretion was greater than the control range in three of the patients. At least one parameter of gastrointestinal function was abnormal in 11 of the 15 patients. Patients with right-sided seminoma had a greater bowel frequency when compared to those with left-sided seminoma (P < 0.05). We conclude that mild abnormalities in gastrointestinal function occur frequently when abdominal irradiation is used to treat stage I seminoma.

Effect of pelvic irradiation on gastrointestinal function: a prospective longitudinal study.

PURPOSE: Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the effects of abdominal and/or pelvic irradiation on gastrointestinal function are poorly defined and treatment is often unsuccessful. To determine both the short- and long-term effects of therapeutic irradiation on gastrointestinal function, we performed a prospective study. PATIENTS AND METHODS: Various aspects of gastrointestinal function were evaluated in 27 patients with potentially curable malignant disease (23 female, 4 male) before the commencement of, during, and 6 to 8 weeks, 12 to 16 weeks, and 1 to 2 years following completion of radiation therapy. Seventeen patients received pelvic irradiation alone and 10 patients received both abdominal and pelvic irradiation. Gastrointestinal symptoms, absorption of bile acid, vitamin B12, lactose, and fat, gastric emptying, small-intestinal and whole-gut transit, stool weight, and intestinal permeability were measured. Results were compared with those obtained in 18 normal volunteers. RESULTS: All 27 patients completed at least 2 series of measurements and 18 patients completed all 5 series of experiments. During radiation treatment, increased stool frequency (p < 0.001) was associated with decreased bile acid and vitamin B12 absorption (p < 0.001 for both), increased fecal fat excretion (p < 0.05), an increased prevalence of lactose malabsorption (p < 0.01), and more rapid small-intestinal (p < 0.01) and whole-gut (p < 0.05) transit. Although there was improvement in most of these changes with time, at 1 to 2 years after the completion of irradiation, the frequency of bowel actions was greater (p < 0.001), bile acid absorption was less (p < 0.05), and small-intestinal transit was more rapid (p < 0.01) when compared with that of baseline and the normal subjects. At this time, at least 1 parameter of gastrointestinal function was abnormal in 16 of the 18 patients. Stool weight was greater (p < 0.05) and whole-gut transit faster (p < 0.01) in patients who received both pelvic and abdominal irradiation, when compared with those who received pelvic irradiation alone. Stool frequency (p < 0.001) and fecal fat excretion (p < 0.05) were greater in those patients who had surgery before radiation therapy. CONCLUSION: Pelvic irradiation is usually associated with widespread, persistent effects on gastrointestinal function.

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.

Acute effects of abdominopelvic irradiation on the orocecal transit time: its relation to clinical symptoms, and bile salt and lactose malabsorption.

Twenty-five patients with abdominopelvic malignant tumors receiving irradiation were studied. The following items were assessed before, during, and at the end of the radiation period: 1) clinical symptoms, scored on the basis of their severity; 2) orocecal transit time (lactulose-H2 breath test); and 3) absorption of lactose and bile salts. Ninety-two percent of the patients showed clinical symptoms suggestive of acute radiation enteropathy, mainly diarrhea. A significant acceleration of the orocecal transit was observed during the study: 70 +/- 6.9 min vs 63.3 +/- 6.3 min vs 44.3 +/- 5.1 min (F = 5.49, p = 0.008), being faster in patients with severe diarrhea (F = 3.25, p = 0.05). Forty-four percent and 57% of the patients developed lactose and bile salt malabsorption, respectively. A decrease in the transit time was observed, independent of the absorption or malabsorption of such substances. However, the orocecal transit was faster in those lactose malabsorbers with severe diarrhea, than in those with mild diarrhea (F = 4.2, p = 0.03). The results suggest that acceleration of orocecal transit may be a major factor in the pathophysiology of radiation-induced diarrhea, whereas lactose malabsorption may contribute to the severity of the diarrhea.