Gerald M. Fraser

Percutaneous endoscopic gastrostomy: high mortality rates in hospitalized patients

OBJECTIVE:Percutaneous endoscopic gastrostomy (PEG) is a widely used method for insertion of a gastrostomy tube in patients who are unable to eat but have a normally functioning gut. Complications have been described, especially in fragile, debilitated patients, and 30-day mortality rates of 4.1–26% have been reported. We assessed the outcome of PEG tube placement for inpatients and outpatients, based on morbidity, mortality, and long-term survival.METHODS:We reviewed the medical records of all patients who underwent PEG at our institution between January 1, 1995 and December 31, 1996. Four groups of patients were compared: Group 1, patients from nursing homes; Group 2, hospitalized patients; Group 3, hospitalized patients matched to Group 2 for diseases, except mental disorder, and not treated with PEG; and Group 4, the general hospital population matched for age.RESULTS:A total of 114 PEG tubes were inserted in 114 patients, 47 from Group 1, 67 from Group 2. Eighty-seven percent of patients in Group 1 underwent PEG because of dementia, versus 46% of Group 2 (p < 0.001). The mortality rate was five times higher in Group 2 than in Group 3 (p < 0.001). The 30-day mortality was seven times higher in Group 2 than in Group 1, twice that in Group 3, and five times higher than in Group 4 (p = 0.002 and p < 0.001, respectively). When intention-to-treat analyses were applied to the data, 19/48 patients died (39.5%) in Group 1, and 60/83 (72.0%) died in Group 2, (p < 0.001).CONCLUSIONS:Patients hospitalized with acute illness are at high risk for serious adverse events after PEG insertion and this procedure should be avoided.

Comparison of two bowel preparations for colonoscopy: sodium picosulphate with magnesium citrate versus sulphate-free polyethylene glycol lavage solution.

Objectives:Adequate preparation of the bowel is essential for accurate colonoscopic examination. We compared colonic preparation with sodium picosulphate plus magnesium citrate (SPS-Mg) with sulphate-free polyethylene glycol electrolyte lavage (PEG-EL) solution before colonoscopy, for quality of bowel cleansing, patient discomfort, and side effects.Methods:Sixty-eight consecutive patients were randomly assigned to receive either 3 sachets of SPS-Mg (16.5 g each) (n = 39) or 3 L of PEG-EL (n = 29) on the day before colonoscopy. Shortly before the procedure each patient was interviewed to determine the degree of discomfort (1 = none or mild, 2 = moderate, 3 = severe) and side effects. The quality of bowel cleansing was graded by a gastroenterologist who was unaware of the method of preparation (from 1 = poor to 4 = excellent).Results:Of the 29 PEG-EL patients, four (14%) did not complete the preparation because of side effects. The degree of discomfort was significantly greater with PEG-EL (mean score, 2.3 ± 0.7) than with SPS-Mg (mean score, 1.4 ± 0.5; p < 0.01). Nausea and vomiting were significantly more common in the PEG-EL group (38%vs 13%; p < 0.05). Using intention-to-treat analysis, bowel cleansing proved to be significantly better with SPS-Mg than with PEG-EL (mean score ± SD, 3.05 ± 0.9 and 2.57 ± 1.0, respectively; p= 0.036).Conclusions:Colonic preparation with SPS-Mg is better tolerated, associated with significantly fewer side effects, and results in higher quality bowel cleansing than preparation with PEG-EL.

Epidemiology of Crohn's disease in Israel: a survey of Israeli kibbutz settlements.

Objective:The prevalence of Crohns disease ranges from 10 to 70 cases per 100,000 population, and is 3–8 times more common among Jews. However, this excess risk is not evident in the Jewish population of Israel. Recently we have described a significant increase in the prevalence and incidence of Crohns disease in the south of Israel. The aim of this study was to confirm this trend in a stable population found in communal (kibbutz) settlements.Methods:We repeated a community-based survey in 124,400 kibbutz residents, 10 yr after our first study. This population represents 5% of the Jewish population of Israel. All Crohns disease patients were located by contacting the kibbutz clinics of the 269 kibbutz settlements (100% compliance). Data was updated to December 31st, 1997, which was designated the point prevalence date, and included information on gender, age, origin, education, profession, extent of the inflammatory process, clinical spectrum of the disease, therapy, complications of the disease, and treatment. The average annual incidence for the 10 yr was calculated from the prevalence data. Only cases with a definite diagnosis of Crohns disease made in a recognized gastroenterology unit were accepted into the study.Results:There were 81 confirmed cases of Crohns disease and the prevalence rate rose from 25.5/100,000 in 1987 to 65.1/100,000 in 1997 (p < 0.001). The mean annual incidence rate for this period (1987–1997) is 5.0/100,000/yr. Prevalence rates were higher in women than men, and in those born in Israel or Europe/America than in Asia/Africa. The mean age at presentation of the disease was lower in 1997 than in 1987, 37.4 ± 17.0 and 45.0 ± 17.0 yr, respectively (p= 0.041). Prevalence was highest in men with >16 yr of education, and in women with 11–12 yr education, 119.7 and 100.3/100,000, respectively.Conclusion:During the decade 1987–1997, the prevalence of Crohns disease has increased in Israel and is approaching the rates in Europe and America.

Epidemiology of ulcerative colitis in Israel : A survey of Israeli Kibbutz settlements

OBJECTIVE:The incidence of ulcerative colitis ranges from 3 to 15 cases per 100,000 persons per year with a prevalence of 50–80 cases per 100,000, and the disease is 3–5 times more common among Jews. In Israel, Ashkenazi Jews have a higher incidence than Sephardi Jews, but a lower incidence than Ashkenazi Jews in the United States or Northern Europe. The aim of this study was to examine the prevalence, mean annual incidence, and clinical patterns of ulcerative colitis in a stable population of communal settlements (kibbutz).METHODS:We repeated a community-based survey in 124,400 kibbutz residents, 10 yr after our first study. This population represents 2.5% of the Jewish population of Israel. All ulcerative colitis patients were located by contacting the kibbutz clinics of the 269 kibbutz settlements (100% compliance). Data were updated to December 31st, 1997, which was designated the point prevalence date, and included information on gender, age, origin, education, profession, extent of the inflammatory process, clinical spectrum of the disease, therapy, complications of the disease, and treatment. The mean annual incidence for the 10 yr was calculated from the prevalence data. Only cases with a definite diagnosis of ulcerative colitis made in a recognized gastroenterology unit were accepted into the study.RESULTS:There were 208 confirmed cases of ulcerative colitis disease, 113 women and 95 men (female:male ratio = 1.19). The prevalence rate rose from 121.0/100,000 in 1987 to 167.2/100,000 in 1997 (p < 0.001). The prevalence rates were higher in women than men. Prevalence was highest in Israeli-born members in 1987 but in European/American-born members in 1997. The average annual incidence rate for the 10-yr period was 5.04/100,000/yr. In 1987, 146 cases of ulcerative colitis were collected. During 10 yr of surveillance 17 patients left the kibbutz, 12 died, and 62 new cases were added. The mean age at presentation of the disease was lower in 1987 than in 1997, 46.14 ± 11.10 and 51.43 ± 16.67 yr, respectively. Prevalence was highest in men with >16 yr and in women with 9–10 yr of education, 259.3 and 242.9/100,000, respectively.CONCLUSIONS:The prevalence of ulcerative colitis in this Israeli population increased and has reached the upper range for European and American populations. The mean annual incidence rate of ulcerative colitis is in the lower range of that reported for the Western countries.

Inflammatory bowel disease: risk factors for adverse pregnancy outcome and the impact of maternal weight gain.

Objective: To identify risk factors for adverse pregnancy outcome in women with inflammatory bowel disease (IBD) and to assess the effect of maternal pre-pregnancy weight and weight gain during pregnancy on pregnancy outcome. Methods: A retrospective, matched control study of all gravid women with IBD treated in a single tertiary center. Data were compared with healthy controls matched to by age, parity and pre-pregnancy BMI in a 3:1 ratio. Results: Overall, 300 women were enrolled, 75 women in the study group (28 with ulcerative colitis and 47 with Crohn’s disease) and 225 in the control group. The rates of preterm delivery and small for gestational age were higher in the study group (13.3 vs. 5.3% p = 0.02 and 6.7 vs. 0.9%, p = 0.004). The rate of cesarean section (36 vs. 19.1%; p = 0.002), NICU admission (10.7 vs. 4.0%, p = 0.03) and low 5-Min Apgar (4.0 vs. 0.4%, p = 0.02) were increased in the study group. Disease activity within 3 months of conception [OR 8.4 (1.3–16.3)] and maternal weight gain of less than 12 kg. [OR 3.6 (1.1–12.2)] were associated with adverse pregnancy outcome. Conclusion: Active disease at conception and inappropriate weight gain during pregnancy are associated with increased adverse pregnancy outcome in patients with IBD.

Preparation for colonoscopy in hospitalized patients

Successful colonoscopy depends on good preparation of the colon before the procedure. Inadequate preparation may lead to cancelled or repeat procedures and compromise patient safety, quality of care, and cost effectiveness. The primary aim of this study was to isolate factors that affect preparation success, especially in older, more severely ill, bedridden patients. The secondary aim was to examine the possible differences in preparation quality between ambulatory and hospitalized patients and the impact of a staff educational program on the preparation of hospitalized patients for colonoscopy. The study group included 303 consecutive ambulatory patients and 104 hospitalized patients referred for colonoscopy between January and March 2002, before the department introduced an educational program on colonoscopy preparation, and 310 ambulatory patients and 105 hospitalized patients referred for colonoscopy between January and March 2003. All patients completed an ad hoc questionnaire, and the findings were compared between ambulatory and hospitalized patients and between patients treated before and after the educational program. Polyethylene glycol was used significantly more often for colonoscopy preparation in hospitalized patients than in ambulatory patients (53.1% versus 8.8%; P=.0001). The hospitalized group was characterized by more incomplete or repeated colonoscopies and poorer preparation quality. On multivariate analysis, the variables found to be independent predictors of good preparation were successful patient completion of the preparatory procedure according to instructions, colonoscopy performed for follow-up after polypectomy, and preparation with sodium phosphate. The educational intervention had no impact on the quality of preparation. In conclusion, sodium phosphate preparation and complete adherence to preparation instructions are the most important factors for successful colonoscopy preparation. Current preparatory methods for hospitalized and severely ill patients need to be revised.

Efficacy of lamivudine in patients with hepatitis B virus precore mutant infection before and after liver transplantation

OBJECTIVE:Hepatitis B virus (HBV) precore mutant infection is associated with a more severe liver disease and a poorer response to interferon. We evaluated the efficacy and tolerance of lamivudine to induce complete and sustained suppression of viral replication in seven patients infected with HBV precore mutant (HBeAg−/HBeAb+/HBV DNA+) (in three patients mutation at codon 1896 was detected by direct sequencing).METHODS:Of the seven patients, five had decompensated HBV cirrhosis in a replicative phase and were liver transplant candidates (Group A) and two patients underwent orthotopic liver transplantation (OLT) for HBV liver cirrhosis and developed recurrent HBV infection in the grafted liver (Group B). Lamivudine 100 mg daily was administered orally for a period of 6–75 wk.RESULTS:After 6–8 wk lamivudine therapy was well tolerated and successfully suppressed HBV replication to an undetectable serum level of HBV DNA by polymerase chain reaction in six patients. In Group A, two patients underwent successful OLT with no evidence of HBV reinfection 2–14 months later. Lamivudine was continued after OLT with no episodes of rejection. Three patients died before a suitable liver could be found (one remained serum HBV DNA+ after 6 wk of lamivudine therapy). In Group B, 9–14 months after lamivudine therapy both patients developed lamivudine resistance (increased liver enzymes, reappearance of serum HBsAg and HBV DNA [by hybridization]). In both patients liver histology had progressed and in both, mutation at codon 552 of the HBV polymerase gene was detected.CONCLUSIONS:Lamivudine is well tolerated in patients with decompensated liver cirrhosis due to HBV precore mutant infection who are liver transplant candidates. In four patients (80%) potent suppression of viral replication was detected, allowing OLT to be performed. However, post-OLT, a resistant mutant developed under lamivudine therapy. Combination therapy with other antiviral agents should be evaluated to discourage the emergence of lamivudine-resistant mutants.

Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease — Case report and literature review

Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid tumors have been reported at increased rates in Crohns disease. We herein report a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel presenting as intestinal obstruction and found incidentally at laparotomy in a 55 year old male with longstanding ileal Crohns disease. We performed a Medline Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of Crohns disease and identified four similar cases. Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed and longstanding Crohns disease, most commonly involved the terminal ileum and presented with symptoms mimicking Crohns disease. Diagnosis was made incidentally at laparotomy in all cases. Lymph node involvement was variable. Clinicians should be aware of this rare entity for expeditious surgical intervention.

Characterization of sodium and chloride conductances in preneoplastic and neoplastic murine colonocytes

Abstractu2002Glucocorticoids, such as dexamethasone, induce amiloride-sensitive Na+ conductances in rat distal colon epithelium. The activity of these conductances diminishes from the surface to the base of the crypt whereas cAMP-stimulated Cl–secretion decreases from the crypt base to the surface. These gradients are likely to be perturbed during carcinogenesis. We therefore determined the magnitude of Na+ and Cl–conductances in colonocytes isolated from normal and carcinogen-treated rats. Colon carcinogenesis was induced by injection of dimethylhydrazine (DMH) (18 mg/kg) for 5 weeks. Before sacrifice animals were treated for 3 days with dexamethasone. Colonocyte populations from the surface to the crypt base (C1–C5) were harvested from the distal colon by a Ca2+-chelating procedure. The activity of Na+ conductances was determined by uptake of 22Na+ by surface and crypt colonocyte populations and by membrane vesicles in the presence and absence of 10 μM amiloride. In control rats Na+ conductance was highest in surface colonocytes and absent in the crypt base. As early as 2 weeks after initiation of DMH treatment amiloride-inhibited Na+ uptake was virtually absent in the upper crypt. Transcriptional assessment of the α-, β- and γ-subunits that constitute the epithelial Na+ channel revealed that DMH treatment reduces the expression of β-subunit mRNA. We then examined 36Cl–efflux from isolated colonocytes of normal and carcinogen-treated rats in response to forskolin (0.01 mM). Forskolin induced a marked rise in cAMP in lower crypt cells concomitant with a significant stimulation of 36Cl–efflux. Intracellular cAMP increased in upper crypt cells in response to forskolin without an increase in 36Cl–efflux. By contrast, upper crypt colonocytes from DMH-treated rats showed forskolin-stimulated efflux beginning 4 weeks after initiation of treatment. We conclude that induction of Na+ conductances by glucocorticoids is inhibited during the early stages of chemical carcinogenesis due to lack of induction of the β-subunit of the channel. By contrast, Cl–transport is stimulated both in surface and lower crypt cell compartments during different stages of chemical carcinogenesis.

Association between Gastric Acid and Mucin Secretion in Dyspeptic Patients

Background and Aims: The maintenance of an intact gastric mucosa implies a balance between aggressive, such as acid, and protective factors such as mucin. We examined gastric aspirates to determine a possible correlation between gastric acid and mucin contents. Methods: Gastric contents were aspirated at gastroscopy in 14 patients. Acid content was evaluated by titration, and mucin content by gel filtration. In 4 other patients these measurements were also performed for 1-hour basal gastric secretion, and after pentagastrin stimulation. Western blot and dot blot for mucin protein were performed with polyclonal antibodies to the protein of MUC 5AC and MUC 6. Results: A positive correlation was demonstrated between acid and mucin content in 14 patients, r = 0.77. In 4 other patients mucin secretion, after pentagastrin injection, increased by 3–46 fold in comparison with basal secretion. A positive correlation was demonstrated between basal acid and mucin secretion, and stimulated acid and mucin secretion. In dot blot experiments, MUC 5AC had a significant higher dot blot intensity than MUC 6. Conclusions: There is a correlation between acid and mucin secretion rates. Secretagogue that causes acid secretion may also cause secretion of protective mucin.