Antonietta Russo

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.

Chronic effects of therapeutic irradiation for localized prostatic carcinoma on anorectal function.

PURPOSE To evaluate prospectively the prevalence and pathophysiology of anorectal dysfunction following radiation therapy (RTH) for localized carcinoma of the prostate. METHODS AND MATERIALS The following parameters of anorectal function were evaluated in each of 35 patients (aged 55-82 years) with localized prostatic carcinoma treated with RTH either to a dose of 55 Gy/20 fractions/4 weeks (18 patients) or 64 Gy/32 fractions/6.5 weeks (17 patients), before RTH and 4-6 weeks and at a mean (+/- SD) of 1.4 (+/- 0.2) years after its completion: (1) anorectal symptoms (questionnaire), (2) anorectal pressures at rest and in response to voluntary squeeze and increases in intra-abdominal pressure (multiport anorectal manometry), (3) rectal sensation (balloon distension) and (4) anal sphincteric morphology (endoanal ultrasound). RESULTS All but 1 patient completed three series of measurements. RTH had no effect on anal sphincteric morphology. The increase in frequency of defecation and fecal urgency and incontinence scores previously reported in the patients 4-6 weeks after RTH were sustained 1 year later (p < 0.001, p < 0.001, and p < 0.05, cf. baseline, respectively). At this time, 56% (19 of 34), 50% (17 of 34) and 26% (9 of 34) of the patients had increased frequency of defecation, fecal urgency, and incontinence, respectively. Decreases in anal sphincteric pressures at rest and in response to voluntary squeeze recorded in the patients 4-6 weeks after RTH were not sustained 1 year later but the volumes of rectal distension associated with perception of the stimulus and desire to defecate were lower compared with baseline volumes (p < 0.01 and p < 0.05, respectively), reflecting heightened rectal sensitivity in the patients. There was no difference in measurements between the two radiation dose regimens. Univariate logistical regression analysis was performed on patients who had experienced increased symptom scores or decreases in recorded motor and sensory manometric parameters at 1 year, cf. baseline. The predictor variables used included individual patient tumor and treatment characteristics as well as individual patient symptom scores and parameters of anorectal motor and sensory function at baseline and 4-6 weeks after RTH. The results of the univariate logistical regression analysis showed that (1) frequency of defecation at 4-6 weeks and (2) rectal volumes at baseline both for (a) perception (p < 0.001) and (b) desire to defecate (p < 0.001), predicted significantly for the patients who had symptoms and signs of anorectal dysfunction at 1 year. Individual patient tumor and treatment-related variables tested, in contrast, had no predictive significance. CONCLUSIONS Anorectal symptoms following RTH for prostatic carcinoma are common and persist at least until 1 year after its completion and are associated with objective evidence of heightened rectal sensitivity.

A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus

PURPOSE To evaluate the natural history of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. SUBJECTS AND METHODS We enrolled 20 patients (6 men, 14 women) with diabetes mellitus (16 with type 1 diabetes, 4 with type 2 diabetes). Each had measurements of gastric emptying of a solid (100 g of ground beef) and liquid (150 mL of 10% dextrose) meal using scintigraphy, glycemic control (glycosylated hemoglobin [HbA(1c)] and mean blood glucose levels), upper gastrointestinal symptoms, and autonomic nerve function at baseline and after a mean (+/- SD) of 12.3 +/- 3.1 years of follow-up. RESULTS There were no differences in mean gastric emptying of the solid component (retention at 100 minutes at baseline: 56% +/- 19% vs. follow-up: 51% +/- 21%, P = 0.23) or the liquid component (time for 50% to empty at baseline: 33 +/- 11 minutes vs. follow-up: 31 +/- 12 minutes, P = 0.71) during follow-up. Mean blood glucose (17.0 +/- 5.6 mmol/L vs. 13.8 +/- 4.9 mmol/L, P = 0.007) and HbA(1c) (8.4% +/- 2.3% vs. 7.6% +/- 1.3%, P = 0.03) levels were lower at follow-up. There was no difference in symptom score (baseline: 3.9 +/- 2.7 vs. follow-up: 4.2 +/- 4.0, P = 0.78). There was evidence of autonomic neuropathy in 7 patients (35%) at baseline and 16 (80%) at follow-up. CONCLUSION In patients with diabetes mellitus, we did not observe any marked changes in either gastric emptying or upper gastrointestinal symptoms during a 12-year period.

Evidence that nitric oxide mechanisms regulate small intestinal motility in humans

Background Non-cholinergic non-adrenergic neural mechanisms involving nerves containing NO have been shown to modulate smooth muscle in the gastrointestinal tract, and it has been suggested that release from tonic NO inhibition may be important in the regulation of cyclical fasting small intestinal motility. Aims To evaluate the role of NO mechanisms in the regulation of fasting small intestinal motor activity in humans using a specific NO synthase inhibitor,N G-monomethyl-l-arginine ( l-NMMA). Methods In seven healthy male volunteers, duodenal and jejunal pressures were measured for four hours with a nine lumen manometric catheter. Volunteers attended on four separate days on which they received an intravenous infusion of either saline or l-NMMA (0.5, 2, or 4 mg/kg/h) in random order. Intravenous infusions began 10 minutes after completion of phase III of the migrating motor complex (MMC). Results The first episode of phase III activity occurred earlier after infusion of 2 and 4 mg/kg/h l-NMMA than after infusion of 0.5 mg/kg/hl-NMMA or saline (mean (95% confidence interval) 52 (36–68) and 57 (18–97) v 116 (69–193) and 145 (64–226) minutes respectively) with a resultant MMC cycle length of 82 (59–105) and 86 (46–126) v 132 (49–198) and 169 (98–240) minutes respectively. The total number of phase III activities during the four hour recording was increased (p<0.05) by l-NMMA at a dose of 4 mg/kg/h (2 (1–3)) but not at 2 mg/kg/h (1.5 (1–2)) or 0.5 mg/kg/h (1.3 (1–2)) compared with saline (1.3 (0.6–2)). l-NMMA had no effect on the duration, velocity, number of contractions per minute, length of migration, or site of origin of phase III of the MMC. The duration of phase I activity was shorter (p<0.05) with 4 mg/kg/hl-NMMA than with saline (12 (1–23)v 31 (19–44) minutes). Conclusions These observations suggest that NO mechanisms play a role in the regulation of fasting small intestinal motor activity in humans.

A retrospective study of the effects of pelvic irradiation for gynecological cancer on anorectal function

PURPOSE To evaluate the prevalence of anorectal dysfunction following therapeutic pelvic irradiation. METHODS AND MATERIALS Anorectal function was evaluated in 15 randomly selected patients (aged 47-84 years) who had received pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5 and 10 years earlier. The following parameters were assessed in each patient: (a) anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in response to rectal distension, voluntary squeeze, and increases in intraabdominal pressure (multiport anorectal manometry with concurrent electromyography of the anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal sphincteric morphology (ultrasound). Results were compared with those obtained in nine female control subjects. RESULTS Ten of the 15 patients had urgency of defecation and 4 also suffered fecal incontinence. Basal anorectal pressures measured just proximal to the anal canal (p = 0.05) and anorectal pressures generated in response to voluntary squeeze measured at the anal canal were less (p < 0.01) in the patients. The fall in anal pressures in response to rectal distension was greater in the patients (p < 0.05) and the desire to defecate occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume relationship in response to rectal distension was greater (p < 0.05) in the patients, suggestive of a reduction in rectal compliance. In 14 of the 15 patients at least one parameter of anorectal motor function was outside the control range. There was no difference in the thickness of the anal sphincters between the two groups. CONCLUSION Abnormal anorectal function occurs frequently following pelvic irradiation for gynecological malignant diseases and is characterized by multiple dysfunctions including weakness of the external anal sphincter, stiffness of the rectal wall, and a consequent increase in rectal sensitivity.

Acute effects of therapeutic irradiation for prostatic carcinoma on anorectal function

Aim—The incidence of anorectal symptoms after radiotherapy (RTH) for localised pelvic malignant disease is unclear. In addition, the effects of pelvic irradiation on both anorectal motility and sensory function are poorly defined. A prospective study was therefore performed on 35 patients (55–82 years of age) with localised prostatic carcinoma before and four to six weeks after RTH to assess its effects on anorectal function. Methods—Anorectal symptoms were assessed by questionnaire. Anorectal pressures at rest and in response to voluntary squeeze, rectal distension, and increases in intra-abdominal pressure were evaluated with perfused sleeve side hole manometry. Rectal sensation was tested during graded balloon distension. Rectal compliance was calculated by the pressure-volume relation obtained during the testing of rectal sensation. Ultrasound was used to determine anal sphincter structure and integrity. Results—RTH had no effect on anal sphincter morphology. The frequency of defecation increased after RTH (7 (3–21) v 10 (3–56) bowel actions a week; p<0.01). After RTH, 16 patients had faecal urgency and eight faecal incontinence, compared with five and one respectively before RTH (p<0.01 for each). Basal and squeeze sleeve recorded pressures were reduced after RTH (54 (3)v 49 (3) mm Hg (p<0.05) and 111 (8)v 102 (8) mm Hg (p<0.01), before and after RTH respectively; means (SEM)). Rectal compliance was reduced after RTH (1.2 v 1.4 mm Hg/ml, p<0.05). After RTH, threshold volumes for perception of rectal distension were lower in the 16 patients who either experienced faecal urgency for the first time (13 patients) or reported worsening of this symptom (three patients) compared with the remaining patients (34 (4)v 48 (5) ml respectively, p<0.05). Conclusion—Faecal incontinence (23%) is a common problem four to six weeks after RTH for prostatic carcinoma and is associated with minor reductions in anal sphincter pressures. The high prevalence of faecal urgency in patients after RTH may be related to alterations in rectal perception of stool.

Gastrointestinal function in chronic radiation enteritis--effects of loperamide-N-oxide.

The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis.

Guar attenuates fall in postprandial blood pressure and slows gastric emptying of oral glucose in type 2 diabetes.

Postprandial hypotension occurs frequently in diabetes; the fall in blood pressure is greatest after ingestion of carbohydrate, particularly glucose and, in type 2 diabetes, is related to the rate of gastric emptying. The aim of this study was to determine whether slowing of gastric emptying by guar gum reduces the fall in blood pressure after oral glucose in patients with type 2 diabetes. Eleven type 2 patients managed by diet alone, age 61.9 ± 1.3 years, had measurements of gastric emptying, blood pressure, blood glucose, and serum insulin on two occasions after ingestion of 300 ml water containing 50 g glucose, with or without 9 g guar gum. The magnitude of the fall in blood pressure was less (P < 0.05) and gastric emptying slower (P < 0.05) after guar. Blood glucose (P < 0.05) and serum insulin (P < 0.01) concentrations were lower after guar. The magnitude of the fall in systolic blood pressure was related to gastric emptying of glucose at 30 min on the control day (r = 0.67, P < 0.05). We conclude that guar gum attenuates the fall in blood pressure after oral glucose in patients with type 2 diabetes mellitus, presumably by slowing glucose absorption.

Effects of Iberogast ® on Proximal Gastric Volume, Antropyloroduodenal Motility and Gastric Emptying in Healthy Men

OBJECTIVE:The herbal preparation Iberogast® has been reported to improve upper abdominal symptoms in functional dyspepsia (FD) and to decrease fundic tone, increase antral contractility, and decrease afferent nerve sensitivity in experimental animals. The effects of Iberogast on the human gastrointestinal tract have not been evaluated.METHODS:We investigated the effects of oral control and Iberogast, each administered as a single dose (1.1 mL), in a double-blind randomized fashion, on proximal gastric volume (part A), antropyloroduodenal motility (part B), and gastric emptying and intragastric distribution of a solid/liquid meal (part C) for 120 minutes, in nine (part A), 12 (part B), and eight (part C) healthy men.RESULTS:Iberogast increased proximal gastric volume (max volume; control 104 ± 12 mL, Iberogast 174 ± 23 mL, P < 0.05) (part A), increased the motility index of antral pressure waves in the first 60 minutes (P < 0.05) without affecting pyloric or duodenal pressures (part B), and slightly increased the retention of liquid in the total stomach between 10 and 50 minutes (P < 0.01), but had no effect on gastric emptying of solids or intragastric distribution (part C).CONCLUSIONS:Iberogast affects gastric motility in humans, probably in a region-dependent manner. The stimulation of gastric relaxation and antral motility may contribute to the reported therapeutic efficacy of Iberogast in FD.

Glucose absorption and gastric emptying in critical illness.

IntroductionDelayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients.MethodsStudies were performed in nineteen mechanically-ventilated critically ill patients and compared to nineteen healthy subjects. Following 4 hours fasting, 100 ml of Ensure, 2 g 3-O-methyl glucose (3-OMG) and 99mTc sulphur colloid were infused into the stomach over 5 minutes. Glucose absorption (plasma 3-OMG), blood glucose levels and GE (scintigraphy) were measured over four hours. Data are mean ± SEM. A P-value < 0.05 was considered significant.ResultsAbsorption of 3-OMG was markedly reduced in patients (AUC240: 26.2 ± 18.4 vs. 66.6 ± 16.8; P < 0.001; peak: 0.17 ± 0.12 vs. 0.37 ± 0.098 mMol/l; P < 0.001; time to peak; 151 ± 84 vs. 89 ± 33 minutes; P = 0.007); and both the baseline (8.0 ± 2.1 vs. 5.6 ± 0.23 mMol/l; P < 0.001) and peak (10.0 ± 2.2 vs. 7.7 ± 0.2 mMol/l; P < 0.001) blood glucose levels were higher in patients; compared to healthy subjects. In patients; 3-OMG absorption was directly related to GE (AUC240; r = -0.77 to -0.87; P < 0.001; peak concentrations; r = -0.75 to -0.81; P = 0.001; time to peak; r = 0.89-0.94; P < 0.001); but when GE was normal (percent retention240 < 10%; n = 9) absorption was still impaired. GE was inversely related to baseline blood glucose, such that elevated levels were associated with slower GE (ret 60, 180 and 240 minutes: r > 0.51; P < 0.05).ConclusionsIn critically ill patients; (i) the rate and extent of glucose absorption are markedly reduced; (ii) GE is a major determinant of the rate of absorption, but does not fully account for the extent of impaired absorption; (iii) blood glucose concentration could be one of a number of factors affecting GE.