Thalidomide as rescue therapy for acute severe ulcerative colitis.

INTRODUCTION: Acute severe exacerbations of Ulcerative Colitis (UC) represent a medical emergency in children and adults. Intravenous steroids remain the first line therapy for this condition, although the steroid refractoriness is common. Second-line therapy, based on the infliximab or thiopurines should be started if no response to corticosteroids is noted. The use of infliximab in children with acute severe UC, nevertheless, does not avoid the colectomy in all cases. METHODS: We present a case of severe acute UC in a paediatric patient successfully treated with thalidomide following the failed treatment with infliximab and a review of the literature. CONCLUSIONS: This is the first case of a patient presenting with acute severe UC who was treated with thalidomide, with favorable evolution. In our case the use of this drug was able to avoid the colectomy that represent the conventional but very invasive recommended therapeutic option of this condition. Therefore, thalidomide may be considered as rescue therapy in selected and carefully monitored cases of acute severe CU.

Association between celiac disease and primary lactase deficiency.

Primary lactase deficiency (PLD) is a common inherited condition caused by a reduced activity of lactase. Two single-nucleotide polymorphisms C/T(-13910) and G/A(-22018) upstream of the lactase gene are associated with lactase nonpersistence. In celiac disease (CD) patients, lactose intolerance could be due to secondary lactase deficiency and to PLD. The aim of this study were to evaluate the association of PLD and CD using genetic test, and to define the prevalence of PLD in celiac subjects compared with a control population. A total of 188 controls and 92 biopsy-proven CD patients were included in the study. More than 70% of all subjects were found homozygous for the polymorphisms. Differences in the prevalence of PLD were not found between CD patients and controls.In conclusions, the hereditary lactase deficiency is frequent in Italian CD children as in control population.

Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay.

BACKGROUND: Some reports highlight the potential application of fecal calprotectin as a direct biomarker of intestinal inflammation and, therefore, as support in choosing candidates for endoscopy. The value of 100 µg/g was recently assumed as the best cutoff for this assay. The purpose of this study was to assess the diagnostic precision of the fecal calprotectin assay, compared to histology, as a stool-screening biomarker for inflammatory bowel disease (IBD) among a group of prospectively identified patients referred for recurrent abdominal pain and altered bowel habits. METHODS: Between 1999 and 2007 we prospectively evaluated the calprotectin assay in a cohort of patients with recurrent abdominal pain and altered bowel habits associated or not with other symptoms suggestive of IBD. All patients suspected of IBD, according to Rome and Porto criteria, provided stool specimens for the calprotectin assay and subsequently underwent endoscopic procedures. RESULTS: Compared to histology, the cutoff of 100 µg/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 µg/g, however, in our series produced the best joint estimate of sensitivity and specificity: 100% and 80%, respectively, with an LR of 5. CONCLUSIONS: In pediatric patients with recurrent abdominal pain and changes in stool habits, a positive calprotectin assay is closely associated with IBD; its systematic employment, therefore, seems to improve the process of endoscopy referral. This test, simple and inexpensive, could be included in the first noninvasive phase of an IBD diagnostic work-up.

Positive impact of blocking tumor necrosis factor alpha on the nutritional status in pediatric Crohn's disease patients.

BACKGROUND: TNFalpha seems to contribute to inflammation and malnutrition in Crohn's disease (CD) patients. In CD patients, the comparative effects on nutritional status of infliximab and traditional therapy have not yet been determined. The aim of our study was to assess the effects of infliximab as compared with those of standard therapy on nutritional status, disease activity, resting energy expenditure (REE), and food intake in CD children and adolescents. METHODS: From September 1999 to September 2005, all CD patients treated with infliximab (group A) were reviewed and matched with CD patients treated with traditional therapy (mesalazine and azathioprine) (group B). RESULTS: Fourteen CD patients from group A and 14 from group B were included; median interval before follow-up investigation was 10 months. Baseline and final values of weight, height, body mass index (BMI), pediatric CD activity index (pCDAI), REE, and food intake were studied. In treated patients, but not in control group, mean baseline weight (kg) and BMI values, 39.7 +/- 13.1 and 17.9 +/- 3.3, respectively, were significantly lower than their final values 42.6 +/- 13.2 and 18.9 +/- 3.1, and median pCDAI values 23.5 were significantly higher than their final values 10 (P < 0.05). Significant changes in height, REE, and food intake were not found in either group. CONCLUSIONS: In pediatric CD patients, infliximab seems to impact positively on the nutritional status as demonstrated by the improvement in weight and BMI, but not in linear growth; effects on nutritional status seem to be due to amelioration of disease activity, rather than to REE reduction or food intake increase.

Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by periods of remission with recurrent episodes of symptom exacerbation because of acute intestinal inflammation, which is correctly evaluated by endoscopy with biopsy sampling. However, many surrogate markers of intestinal inflammation, including fecal calprotectin (FC), are detected as potential predictors of mucosal inflammation in IBD patients. The aim of our study was to retrospectively assess the clinical efficacy of the calprotectin assay in determining histological relapses of pediatric IBD patients. METHODS: We retrospectively reviewed the histological examinations, clinical records, and FC values of patients who had undergone colonoscopy at our hospital over an 8-year period, from December 31, 1998, to December 31, 2006. Only patients with a first histological examination showing a quiescent IBD who submitted to a second histological examination during the next 3 years were selected. RESULTS: Seventy-three IBD patients, all with a first biopsy showing a quiescent IBD, were studied; at the second histological examination, 32 presented with relapse and 41 presented with remission. Relapsed patients showed significantly increased FC levels compared with nonrelapsed patients. A FC value of 275 mug/g achieved sensitivity and negative predictive value of 97% and specificity and positive predictive value of 85% in predicting histological relapse. CONCLUSIONS: FC seems to be a direct measure of intestinal inflammation and therefore a good marker of the risk of histological relapse in pediatric IBD patients. The application of this test in clinical practice may enable the avoidance of invasive tests as well as targeting treatment.

Chronic constipation in hemiplegic patients.

AIM: To assess the prevalence of bowel dysfunction in hemiplegic patients, and its relationship with the site of neurological lesion, physical immobilization and pharmacotherapy. METHODS: Ninety consecutive hemiplegic patients and 81 consecutive orthopedic patients were investigated during physical motor rehabilitation in the same period, in the same center and on the same diet. All subjects were interviewed >= 3 mo after injury using a questionnaire inquiring about bowel habits before injury and at the time of the interview. Patients' mobility was evaluated by the Adapted Patient Evaluation Conference System. Drugs considered for the analysis were nitrates, angiogenic converting enzyme (ACE) inhibitors, calcium antagonists, anticoagulants, antithrombotics, antidepressants, anti-epileptics. RESULTS: Mobility scores were similar in the two groups. De novo constipation (OR = 5.36) was a frequent outcome of the neurological accident. Hemiplegics showed an increased risk of straining at stool (OR: 4.33), reduced call to evacuate (OR: 4.13), sensation of incomplete evacuation (OR: 3.69), use of laxatives (OR: 3.75). Logistic regression model showed that constipation was significantly and independently associated with hemiplegia. A positive association was found between constipation and use of nitrates and antithrombotics in both groups. Constipation was not related to the site of brain injury. CONCLUSION: Chronic constipation is a possible outcome of cerebrovascular accidents occurring in 30% of neurologically stabilized hemiplegic patients. Its onset after a cerebrovascular accident appears to be independent from the injured brain hemisphere, and unrelated to physical inactivity. Pharmacological treatment with nitrates and antithrombotics may represent an independent risk factor for developing chronic constipation.

Long-term treatment with autologous red blood cells loaded with dexamethasone 21-phosphate in pediatric patients affected by steroid-dependent Crohn disease.

BACKGROUND: Inflammatory bowel disease (IBD) present in childhood in 15% to 25% of cases. The aim of therapy in children is not only to guarantee normal growth but also to prevent relapse and to maintain remission. Steroids are effective to induce remission; however, resistance, dependency, and irreversible side effects can develop. The aim of this study was to determine whether treatment with repeated infusions of autologous red blood cells (RBCs) loaded with dexamethasone 21-phosphate (Dex 21-P) is safe and allows maintenance of long-term remission in children with steroid-dependent Crohn disease (CD). PATIENTS AND METHODS: Eighteen consecutive pediatric patients who met the inclusion criteria were admitted to the study. Infusions of autologous RBCs loaded with Dex 21-P were performed every 4 weeks; the mean duration of treatment was 24 months. At the beginning of treatment and after 6, 12, and 24 months, we performed clinical evaluation according to the Pediatric Crohn Disease Activity Index (pCDAI). Assessment of body mass in dexamethasone and bone mineral density by means of computerized bone mineralometry-dual energy x-ray absorptiometry, endoscopic evaluation, and hematic morning cortisol determination were also performed. RESULTS: During treatment, the mean pCDAI significantly decreased (P < 0.05); 78% of patients discontinued steroids. Determination of morning cortisol showed suppression only on the first day after infusion, followed by normalization of values. Endoscopic findings showed remission in 44% of patients. None of the patients experienced serious side effects. CONCLUSIONS: These data suggest that repeated infusions of RBCs loaded with Dex 21-P can be safe and useful to maintain long-term remission in pediatric patients with moderately active CD.

Long-term parenteral nutrition in pediatric autoimmune enteropathies.

Severe and protracted or persistent diarrhea (SPD) is the most severe form of diarrhea in infancy and has also been defined as intractable diarrhea when it leads to dependence on total parenteral nutrition (TPN). One of the rare causes of SPD is represented by autoimmune enteropathy that is characterized by life-threatening diarrhea mainly occurring within the first years of life, persistent villous atrophy in consecutive biopsies, resistance to bowel rest, and evidence of antigut autoantibodies. We evaluated 10 patients (seven boys, mean age at diagnosis 18 months; range: 0 to 160 months) fulfilling criteria of autoimmune enteropathy to assess dependence on TPN. TPN was first required in all patients to avoid dehydration and electrolytic imbalance. All patients were dependent on immunosuppressive therapy (steroid, azothioprine, cyclosporine, tacrolimus). Three patients died of sepsis: two during TPN while in the hospital, and one at home after he was weaned off TPN. Five patients are weaned off TPN after a mean period of 18 months; they are actually on oral alimentation with a cow milk-free diet after a period of enteral nutrition with elemental formula. One underwent total colectomy and bone marrow transplantation and one developed an IPEX syndrome. One patient is still dependent on TPN for 24 months. She is on home parenteral nutrition. Patients with diagnosis of IPEX syndrome require parenteral support with three or four infusion per week. TPN represents a fixed step in the management of autoimmune enteropathy, but it may be considered as an interim treatment while waiting for intestinal adaptation, at least in some selectioned case of autoimmune enteropathy. Bone marrow transplantation should be considered and reserved for those patients with severe complications due to home parenteral nutrition, or in those that are really dependent on parenteral nutrition.

Gastric electric activity assessed by electrogastrography and gastric emptying scintigraphy in adolescents with eating disorders.

BACKGROUND: Patients with eating disorders can refer to a variety of gastrointestinal symptoms, sometimes to justify reduced food intake and vomiting. The authors investigated whether adolescent patients with eating disorders and dyspeptic symptoms have altered gastric electric activity and abnormal gastric emptying as assessed respectively by electrogastrography and scintigraphy. METHODS: Twenty-eight patients (18 with anorexia and 10 with bulimia) and 16 healthy volunteers underwent electrogastrography; 20 of the 28 patients (14 with anorexia and 6 with bulimia) underwent gastric emptying scintigraphy. Electrogastrography with bipolar recording lasted 1 hour, 30 minutes before and after a standard meal. Before gastric emptying scintigraphy, patients fasted overnight; during testing, they ingested a solid meal labeled with technetium-99m sulfur colloid. The ratio of fasting to postprandial electrogastrographic variables was evaluated using the Wilcoxon matched-pair test. The Mann- Whitney test was used to compare absolute values for electrogastrographic data in each group. The Student paired t test was used to compare scintigraphic results expressed as percentage of gastric emptying at 60 minutes and as the gastric emptying time (T(1/2)). RESULTS: Patients with bulimia significantly differed from those with anorexia and control subjects regarding the amount of normal gastric electric activity and bradygastria, and from patients with anorexia only regarding tachygastria. These electrogastrographic variables did not differ significantly between patients with anorexia and control subjects. Gastric emptying time (T(1/2)) was significantly longer in patients with bulimia than in those with anorexia. CONCLUSIONS: Adolescent patients with bulimia who complain of dyspeptic symptoms have documentable abnormalities of gastric electric activity and emptying, whereas their counterparts with anorexia, probably owing to their shorter disease duration, do not.

Role of electrogastrography in detecting motility disorders in children affected by chronic intestinal pseudo-obstruction and Crohn's disease.

Gastrointestinal motility disorders are frequently found in several pathologies. The aim of this study was to assess, by means of electrogastrography, the presence of gastrointestinal motility abnormalities in children affected by Crohn's disease (CD) or Chronic Intestinal Pseudo-Obstruction (CIPO). Patients and Methods. We studied 34 subjects; 20 control subjects (M = 15, mean age = 10 +/- 3.5 yrs), 8 patients (M = 4, mean age = 18 +/- 7 yrs) with Crohn's disease in a quiescent phase and 6 patients (M = 6, mean age = 10 +/- 3.5 yrs) with Chronic Intestinal Pseudo-Obstruction. Results. Analysis of gastric electrical activity (GEA) parameters demonstrated that in the control group physiological post-prandial changes are represented by an increase of 3 Cycles Per Minute (3 CPM) activity, Period Dominant Power (PDP) and Period Dominant Frequency (PDF) and by the reduction of bradygastria. Crohn patients showed an insignificant increase of 3 CPM and PDP; CIPO patients showed an abnormal variation of 3 CPM, PDP and post-prandial bradygastria. Moreover, CD patients showed a significant difference in post-prandial values of PDP compared to normal subjects. CIPO patients revealed a significant difference in the values of either preprandial PDF with tachygastria or the post-prandial value of 3 CPM, compared to normal subjects. Conclusions. EEG is a non-invasive method to study gut motility related to GEA alterations present in CIPO as well as in CD patients.

Preliminary report of electrogastrography in pediatric gastroresection: can it be predictive of alteration of gastric motility?

BACKGROUND/PURPOSE: Gastric resection is an infrequent surgical procedure in childhood. However, the use of the stomach for bladder augmentation and substitution is well documented. Partial gastrectomy performed in gastrocystoplasty (GCP) involves the greater curvature of the stomach, the same area in which gastric pace-maker cells are known to be placed. The aim of this study was to assess, by electrogastrography (EGG), if subtotal gastric resection can alter gastric motility in children submitted to partial gastrectomy for GCP. METHODS: Gastric electrical activity (GEA) was evaluated in 25 children using EGG: 10 patients (4 boys, 6 girls; mean age, 11.6 years) previously submitted to GCP, and 15 normal subjects (12 boys, 3 girls; mean age, 8.62 +/- 2.77 years) as controls. All patients were submitted to cutaneous EGG; recording GEA for 30 minutes before and after a standard test meal. The percentage of 3 cycles per minute (3CPM), bradygastria, tachygastria, DFIC (dominant frequency instability coefficient), DPIC (dominant power instability coefficient), PDP (period dominant power), PDF (period dominant frequency) were recorded and analyzed using Wilcoxon matched-pair test. Data were considered statistically significant if P <.05. RESULTS: Normal subjects as well as operated patients showed a statistically significant difference in bradygastria (P =.05), PDP and PDF (P =.05) percentage, comparing pre versus postprandial period. In the normal group, 3CPM (P =.0012) and DFIC (P =.0008) were statistically different between the pre- and postprandial period. Patients who underwent GCP did not show any statistically significant difference in 3CPM and DFIC pre- and postprandial. CONCLUSIONS: In normal subjects, GEA showed a complete variation after the meal, whereas in operated patients GEA was impaired and only partially modified after the meal. This observation suggests that in patients with gastric resection, adaptation of the stomach to food ingestion is present but incomplete with respect to normal subjects; it can be caused by surgical removal of the pace-maker cells of the greater curvature. For this reason a follow-up analysis of gastric function is recommended for all patients undergoing GCP.

Anorectal function in multiple system atrophy and Parkinson's disease.

This study was designed to investigate anorectal function in Parkinson's disease and multiple system atrophy (MSA). After a standardized interview, 17 patients with Parkinson's disease (PD) and 16 patients with multiple system atrophy (MSA) underwent anorectal manometry with a continuously perfused multi-lumen catheter, located to record pressures from the anal canal, and a balloon for rectal distension. Data were analyzed by observers blind to the neurologic diagnosis. Disease duration was shorter in the MSA than in the PD group (6+/-4 versus 10+/-5 yrs, p<0.05). Most patients reported a bowel frequency of less than three evacuations per week and some patients had fecal incontinence. Most manometric recordings disclosed an abnormal pattern during straining (a paradoxic contraction or lack of inhibition) in 13 patients with MSA and 11 patients with PD. Mean anal pressures and rectal sensitivity threshold were not significantly higher in the MSA group, whereas the inhibitory anal reflex and rectal compliance thresholds were within the normal range in both groups. Manometric patterns did not differentiate patients with MSA from patients with PD. Most patients in both groups showed an abnormal straining pattern, decreased anal tone, or both dysfunctions. In conclusion, our findings suggest that although bowel and anorectal dysfunctions do not differentiate MSA from PD, both abnormalities occur earlier and develop faster in MSA than in PD.

Sequential treatment of chronic constipation in paraplegic subjects.

Chronic constipation is the main gastrointestinal complaint of spinal cord injury (SCI) patients, and has a significant effect on patients' lives, concerning nursing dependence, morbidity and complications. Many therapies have been proposed to treat chronic severe constipation, most of them with limited effect or being unpredictable in their effect or being expensive or very radical. Ten spinal cord injury patients have been submitted to a therapeutic protocol based on a high residue diet, a standardised water intake, and on the use of a sequential schedule of evacuating stimuli. After four weeks of treatment the patients showed an increased frequency of bowel movements per week, a decreased total gastrointestinal transit time, and a decreased need for oral and rectal laxatives. This treatment seems to be effective in modifying patients' bowel habits, and therefore could be considered as a standardised protocol for the management of severe constipation in those who are paraplegic.

Palliative treatment of extrahepatic bile ducts tumors.

Extrahepatic bile duct (EHBD) tumors often become symptomatic in an advanced stage when curative resection is seldom possible. In a group of 111 patients, 7 (6.3%) received no treatment, 32 (28.8%) underwent non-operative biliary drainage (NOD), and 72 (64.8%) underwent surgical exploration. Radical resection was possible in only 25 cases (34.7%); 14 patients (19.4%) underwent a biliary digestive bypass (BDB), 15 (20.8%) received a transtumoral biliary prosthesis (TBP), and 18 (25.0%) an external biliary drainage (EBD). Average survival rates were: 6.5 months after BDB, 4.0 months after TBP, and 2.8 months after EBD. In a second group of 2,066 patients with primary and secondary malignant obstruction of the upper EHBD, treated with the insertion of a Carey-Coons transhepatic transtumoral biliary prosthesis, the average survival was 4.3 months. The early morbidity rate was 0.6%. Obstruction of the prosthesis occurred in 91 patients (4.4%), and the late morbidity rate was 3.6%. Although EHBD tumor treatment results are generally poor, surgical exploration should be performed in all patients with acceptable surgical risk, and without evidence of disseminated disease. When resection of the tumor is not feasible, we favor the use of a BDB or of a biliary prosthesis over that of an external drainage. In poor risk cases or cases with evidence of disseminated disease, we prefer the placement of an internal prosthesis (PTBD or endoscopic.

[Lymphovenous anastomosis in severe ascites]. / L'anastomosi linfovenosa nell'ascite difficile.

The authors dealt with 37 patients suffering from advanced liver cirrhosis with ascites. Eighteen patients out of them underwent Denver peritoneum-jugular shunt as a first choice procedure, the other 19 patients underwent lymphovenous anastomosis. The extremely advanced hepatic damage and the general conditions of these patients discouraged us to perform a portocaval shunt. In the 19 patients who underwent lymphovenous anastomosis we had no mortality rate. Two patients showed post-operative complications: 1 patient complained which hoarseness regressed in 5 months and the other patient suffered from a spleno-mesenteric-portal thrombosis with digestive hemorrhage from gastro-esophageal varices. In 6 patients out of 19 who underwent lymphovenous anastomosis, we did not obtain any immediate positive effects on ascites. In 4 patients, after 3 months, the ascites came back ingravescent and in the other 9 patients the positive effects on ascites were still evident after 1 year. Despite failure to obtain very comforting results, they suggest to employ this technique at any rate, as the first procedure, to make ascites more "manageable", because of its safety.

[The Denver peritoneojugular shunt. Current indications]. / Shunt peritoneo-giugulare sec. Denver. Attuale indicazione.

Personal experience of 31 patients suffering from intractable ascites due to advanced liver cirrhosis between 1978 and 1987 is reported. Seventeen patients were selected for a peritoneojugular shunt: in 3 patients the Le Veen shunt was performed and in 14 the Denver shunt was preferred. The high postoperative morbidity and mortality due to liver failure, DIC, hepatorenal syndrome, bleeding, sepsis and cerebral thrombosis is pointed out. Careful selection of patients to be submitted to this surgical procedure is essential because of the high morbidity due to ascites reinfusion. DIC has to be diagnosed as soon as possible and, when severe, the prompt interruption of the peritoneojugular shunt is mandatory.

Effect of somatostatin in controlling bleeding from esophageal varices.

A multicenter double-blind clinical trial was undertaken to evaluate the efficacy of a short-term somatostatin treatment versus a short-term vasopressin treatment on acute hemorrhage from esophageal varices in patients with liver cirrhosis and portal hypertension. Forty-nine patients with massive hemorrhage and endoscopic diagnosis of bleeding esophageal varices completed the study. Patients were randomly assigned to somatostatin treatment (24 patients: 250 micrograms/hr i.v. for 48 hrs) or vasopressin treatment (25 patients: 0.1 U/min i.v. for 48 hrs). The Sengstaken-Blakemore tube was utilized, when needed, for a six hour period. In case of failure the patients were crossed-over to the other treatment. Patients in whom the bleeding stopped at 48 hrs, were randomly assigned to somatostatin (250 micrograms/hr i.v.) or placebo for seven days. Bleeding stopped in 68% of patients treated with somatostatin and in 28% of patients treated with vasopressin (p less than 0.0013). Mortality rate was lower, but not significantly so, in the somatostatin group compared to the vasopressin group. No differences were noted between somatostatin and placebo in preventing bleeding recurrences. These data suggest that somatostatin, when combined if necessary with a 6 hour period of balloon tamponade, is more effective than vasopressin at low doses in controlling severe hemorrhage from esophageal varices in patients with liver cirrhosis and portal hypertension. A clinical use of somatostatin seems to be indicated in these patients.

Biliary secretion of phosphatidylcholine and its molecular species in cholecystectomized T-tube patients: effects of bile acid hydrophilicity.

The aim of the present study was to establish whether the oral administration of bile acids with different hydrophilic properties affects the amount of phosphatidylcholine as well as the pattern of PC molecular species secreted in bile. We studied the biliary output of total and individual PC species in cholecystectomized T-tube patients, with a total biliary outflow, after oral administration of 750 mg of ursodeoxycholate (3 patients) or deoxycholate (3 patients). The latter experiments were repeated after 3 days of taurine supplementation (1500 mg daily) in order to increase, by means of the tauro-conjugation, the hydrophilicity of the secreted BA. A linear function was observed, during all the studies, between BA and PC biliary secretion, but the amount of PC secreted per mole of BA was higher for the less hydrophilic BA, such as deoxycholate, than for the more hydrophilic ursodeoxycholate or during deoxycholate plus taurine experiments. With regard to the pattern of PC molecular species, we observed no changes after administration of ursodeoxycholate. An increase in the secretion of the major polyenoic species (i.e., 16:0-18:2 and 16:0-20:4), with respect to the secretion of the monoenoic, was revealed during deoxycholate experiments. Conversely, during the deoxycholate plus taurine experiments, the secretion of the major monoenoic PC species (i.e., 16:0-18:1) increased more than that of the polyenoic species. We suggest that the observed modifications of the pattern of PC molecular species, secreted in bile, represent the result of a physicochemical effect of BA on liver membranes.