Strategy for colorectal cancer screening.

Colorectal cancer is a leading cause of cancer death in Israel. Our current understanding of the colorectal adenoma-carcinoma sequence has led to the use of screening for timely detection of polyps and cancer. Digital examination of the rectum is a test that can be performed by all doctors. Fecal occult blood testing, flexible sigmoidoscopy and colonoscopy are the standard screening techniques for patients. Computerized tomography colonography is now entering this field. This review discusses the merits and uncertainties of these strategies as related to the risk of colorectal cancer in selected populations.

Cystic fibrosis transmembrane conductance regulator and Na+ channel subunits mRNA transcripts, and Cl- efflux, show a different distribution in rat duodenum and colon.

AIM: We compared the distribution and putative association of Cl- channel transport, CFTR mRNA transcripts, and Na+ channel (ENaC) alpha- and beta-subunit mRNA transcripts in villus and crypt epithelial cells of duodenum, with corresponding surface and crypt cells of colon from sodium-depleted rats. METHODS: Cells were loaded with 36Cl- and forskolin-stimulated efflux was determined. RT-PCR was performed for CFTR mRNA transcripts and ENaC alpha- and beta-subunit mRNA. Duodenal epithelial cell response to VIP was assessed by measuring intracellular cAMP. RESULTS: Forskolin-stimulated Cl- efflux occurred with decreasing magnitude in duodenal crypt, duodenal villus, colonic crypt and colonic surface cells in Na(+)-depleted animals. CFTR expression was correlated directly with Cl- efflux (r=0.91, P<0.01). Na+ channel alpha-subunit was expressed in colon and duodenum in animals fed diets with a high or low sodium content. While the beta-subunit mRNA was detected in the colon of sodium-restricted rats, it was absent in the duodenum under control conditions and after Na+ restriction. There was an inverse correlation between mRNA transcripts for CFTR and the ENaC alpha-subunit (r=-0.93, P<0.003) and beta-subunit (r=-0.91, P<0.004) in colon. VIP-stimulated cAMP in duodenal epithelial cells was greater in crypt than villus (P<0.05). CONCLUSION: Cl- efflux, CFTR transcription and forskolin-stimulated cAMP activity occur in both crypt and villus epithelial cells in duodenum. Possible interaction between CFTR and Na+ channels is apparently limited to parts of the colonic crypt. Lack of duodenal beta-subunit expression makes ENaC activity unlikely.

Does insertion of a rectal tube after colonoscopy reduce patient discomfort and improve satisfaction?

BACKGROUND: Distention of the colon is a major contributor to patient discomfort after colonoscopy. Some physicians and nurses believe insertion of a rectal tube relieves this discomfort and improves patient satisfaction with the procedure. This prospective, randomized, controlled trial assessed rectal tube insertion for reduction or prevention of abdominal bloating and discomfort after colonoscopy. METHODS: One hundred fifty-seven patients were prospectively randomized to groups with (n = 68) and without (n = 89) rectal tube insertion after colonoscopy. Patients were evaluated for bloating, discomfort, and pain before the procedure, at its conclusion, at discharge, and 24 hours later (by telephone). Satisfaction was also assessed at discharge and 24 hours later. RESULTS: There were no differences between groups with respect to age, gender, hospitalization status, comorbidity, or socioeconomic status. In both groups the cecum was reached in 90% of patients and procedure time was similar. There were no differences between the groups in abdominal bloating (patient and nurse assessment), abdominal discomfort, or satisfaction at any time point. There were no serious complications. The subgroup of patients who experienced more severe pain and discomfort, regardless of whether a rectal tube was inserted, was characterized by more complaints of bloating, more incomplete procedures, and a higher rate of previous abdominal operations. CONCLUSIONS: Insertion of a rectal tube after colonoscopy does not affect abdominal bloating, pain, or discomfort during recovery from the procedure or over the subsequent 24 hours, nor does it affect overall patient satisfaction.

Gastroduodenal pathophysiology of NSAIDS. Short summaries of the slides.

We need to learn a lot more about the pathophysiology of NSAIDs, especially COX-2, which at present are the drugs of choice.

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Fibromyalgia in inflammatory bowel disease.

OBJECTIVE: Studies of the rheumatological complications of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) have focused on peripheral arthritis and spondylitis, and less is known about soft tissue rheumatism, specifically the fibromyalgia syndrome (FM). Our aim was to estimate the prevalence of FM and assess pain thresholds in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seventy-two patients with UC and 41 with CD attending consecutively at the Gastroenterology Outpatient Clinic were assessed for the presence of FM and tenderness thresholds. FM was diagnosed according to the American College of Rheumatology 1990 criteria. Tenderness was measured by manual palpation and with a dolorimeter. One hundred twenty healthy subjects served as controls. RESULTS: FM was documented in 30 of 113 patients with IBD (30%), specifically in 49% of patients with CD and 19% with UC (p = 0.001); in controls the rate was 0%. Subjects with CD exhibited more tenderness and reported more frequent and more severe FM associated symptoms than subjects with UC. Patients with CD had a higher tender point count, 11.3 (+/- 6.5), than those with UC, 6.4 (+/- 5.7) (p = 0.001); in healthy controls, the count was 0.1 (+/- 0.5). Tenderness thresholds (kg) were lower in CD 2.9 (+/- 1.7) than UC 3.9 (+/- 2.0) (p = 0.005) and controls 5.8 (+/- 0.9). CONCLUSION: FM is common in IBD, particularly Crohn's disease. The lower pain threshold in Crohn's disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.

Premedication with Xylocaine spray does not lead to a false positive rapid urease test.

Rapid urease tests are used for quick identification of Helicobacter pylori during upper gastrointestinal endoscopy. Rapid urease test solutions contain urea, which in the presence of H. pylori urease, generates ammonia, which changes the test medium color to indicate a positive result. Theoretically, Xylocaine spray (ASTRA, Södertalje, Sweden), which has a basic pH value, could cause a similar positive reaction in the test medium. To determine whether patients premedicated with Xylocaine spray have a higher rate of false positive urease tests, we compared the results of a rapid urease test and histologic stains in 107 patients, 54 premedicated with Xylocaine spray and 53 premedicated with intravenous midazolam but not Xylocaine spray. There were no significant differences in test sensitivity, specificity, or predictive values between the study groups. We conclude that patients can be premedicated with Xylocaine spray without concern that the false positive rate of rapid urease tests will increase.

Increased non-articular tenderness in patients on steroid therapy.

Increased non-articular tenderness and tender shins have been suggested to be associated with steroid therapy in patients with lupus. The aim of the present study was to extend this observation in a different disease, inflammatory bowel disease (IBD), and to examine the relationship between tenderness, dosage and duration of steroid therapy. Eighty-seven patients with 11313, 23 of them on steroid therapy, were assessed for disease activity and nonarticular tenderness. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at four shin sites, nine tender point sites and four control point sites. Patients on steroids were significantly more tender than subjects not on steroids: their mean tender point counts were 13.3 and 6.7 (p < 0.001), respectively, and the dolorimetry thresholds at all three sites were significantly lower in the steroid group (p < 0.001). Increased tenderness was also associated with increased steroid dosage. However, tenderness was not related to duration of steroid therapy, to gender, or to previous steroid therapy being discontinued at least a year ago. Disease activity was neither related to tenderness nor to steroid treatment. The demonstration of increased tenderness in IBD patients on steroid therapy, in addition to earlier observations in lupus, may suggest that such a relationship is not disease specific. The recognition of this association is important to physicians treating patients with steroids and will prevent misinterpretations of complaints about tender shins and diffuse tenderness as part of the disease entity itself.

Open access endoscopy for hospitalized patients.

OBJECTIVES: Most requests for gastroenterology consultations for hospitalized patients are for endoscopic procedures. Open access endoscopy has been evaluated in several institutions for outpatients. Our aim was to evaluate an open access policy for hospitalized patients. METHODS: Since April of 1996, patients hospitalized in the Soroka Medical Center have been referred directly for upper endoscopy (esophagogastroduodenoscopy, EGD) and flexible sigmoidoscopy (FS). The numbers of procedures and consultation requests between July 1, 1996, and September 30, 1996, were compared with the corresponding months of 1995. A survey of physician satisfaction with the new open access system was conducted. RESULTS: The mean number of monthly consultations during the study period was 30.7 +/- 2.4, compared with 119.3 +/- 5.4 during the same months in 1995 (p = 0.006). Open access endoscopy was performed on 114 patients during the study period. Upper GI bleeding (n = 41) and abdominal pain (n = 33) were the most common indications for EGD. There were nine duodenal ulcers, five gastric ulcers, and eight gastric carcinomas. Sixteen patients (21%) had normal EGDs. The most common indications for FS were rectal bleeding (n = 24) and diarrhea (n = 13). Seven patients had colorectal cancer; 12 FSs were normal. In all, 286 EGDs and FSs were conducted in the study period compared with 253 in 1995 (not significant). All physicians expressed satisfaction with the new system and favored its continuation. CONCLUSIONS: The open access policy for hospitalized patients led to a considerable reduction in requests for consultations, with no significant increase in the number of endoscopies. The majority of patients referred directly for endoscopy had appropriate indications.

Role of protein kinase C in duodenal mucosal bicarbonate secretion in the guinea pig.

Since duodenal bicarbonate secretion (DBS) is increased by m-cholinoceptor agonists, it was postulated that protein kinase C (PKC) has a role in this secretion. This premise was examined in guinea pigs, using 12-O-tetradecanoyl-phorbol 13-acetate (TPA) to stimulate bicarbonate production in the perfused duodenum in vivo, and to activate PKC in isolated duodenal enterocytes. TPA (10(-7) mol.kg-1) infused intravenously stimulated active DBS from basal values of 3.64 +/- 0.66 to 8.73 +/- 1.59 mumol.cm-1.10 min-1. This effect was completely blocked by verapamil (4 x 10(-7) mol.kg-1). PKC activity in duodenal enterocytes in the basal state was most abundant in the cytosolic fraction (2,221 +/- 444 U/mg protein) and very low in the particulate fraction (227 +/- 51 U/mg protein). TPA (10(-7) mol.kg-1) caused a time-dependent translocation of the cytosolic, lipid-dependent activity of PKC into the particulate fraction. The effect was maximal at 5 min incubation and was reversed by 30 min. In the particulate fraction, this activity was no longer lipid-dependent, but could be stimulated by Ca2+ alone. These data support the hypothesis that translocation of PKC may contribute to DBS.

Bicarbonate secretion in the guinea pig duodenum: functional characterization of peptide hormone receptors in duodenal enterocytes.

To get information about the peptide hormone receptors involved in duodenal bicarbonate secretion (DBS) and their cellular location, we determined DBS and adenylate cyclase (AC) activity in response to hormones of the vasoactive intestinal polypeptide (VIP)/secretin family of peptides. DBS was determined in an isolated, perfused (24 mmol/1 NaHCO3) loop of the proximal duodenum in urethane- and indometacin-treated guinea pigs. AC stimulation was measured in isolated, homogenized duodenal enterocytes, the histological evaluation of which revealed their villous origin. VIP (10(-9) to 10(-7) mol x kg-1) dose-dependently increased DBS 3.5-fold (p < 0.01); this effect was completely inhibited by the VIP antagonist [D-p-Cl-Phe6,Leu17]VIP (10(-6) mol x kg-1). Glucagon (10(-8) to 10(-6) mol x kg-1) increased DBS 2.1-fold, while secretin (10(-9) to 10(-6) mol x kg-1) had no effect on DBS, but stimulated pancreatic bicarbonate secretion. VIP concentration-dependently increased AC activity 5.6-fold with an EC50 of 1.3 x 10(-9) mol/l. [D-p-Cl-Phe6,Leu17]VIP caused a rightward shift of the VIP concentration-response curve. A Schild plot analysis yielded a slope of 0.85 +/- 0.11, indicating competitive inhibition. While secretin also stimulated AC activity, although 1,000-fold less potent than VIP, glucagon was ineffective. These data indicate that specific VIP receptors, which mediate VIP-stimulated bicarbonate secretion, are present on villous enterocytes. Stimulation of AC by secretin seems to be of pharmacological relevance only and is consistent with the lack of effect of this hormone on DBS. Glucagon likely activates a second transmitter of bicarbonate secretion, or works independently of AC.

A controlled double blind multicenter study of the effectiveness of 5-aminosalicylic acid in patients with Crohn's disease in remission.

We evaluated the efficacy of an oral formulation of 5-amino-salicylic acid in lowering the relapse rate after remission of Crohn's disease. Included were 59 patients who had proven Crohn's disease of at least 1 year's duration, and who had been in continuous remission for at least 6 months, while taking only 5-aminosalicylic acid or no therapy at all. Remission was defined as a Harvey Bradshaw index score (Softley-Clamp modification) of < 4. Patients were given coded mesalzaine 250 mg or placebo tablets (2 x 2 day). They were seen at 0, 1, and 2 months, and then every 2 months until the end of the study. Trial endpoints were 1 year of follow-up, or clinical relapse results. After randomization, 31 patients were included in the placebo arm, and 28 in the treatment arm. There were no significant differences between the two groups at entry. Ten patients were withdrawn from the trial because of noncompliance, loss of follow-up, or headache. There were more clinical relapses in the placebo arm (15 patients, 55%) than in the treatment arm (6 patients, 27%) (p < 0.05). Mesalazine had a significant advantage over placebo (p < 0.05) only in the subgroups of patients with ileal Crohn's disease and in those older than 30 years. We conclude that mesalazine has a moderate but significant benefit in preventing relapse in Crohn's disease in remission; this occurred only in patients with small-bowel involvement or in those older than 30 years.

Effect of somatostatin-14 on duodenal mucosal bicarbonate secretion in guinea pigs.

The role of somatostatin-14 in duodenal mucosal HCO3- secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO3- output from the isolated, perfused (24 mM NaHCO3 + 130 mM NaCl) proximal duodenum was measured during intravenous infusion (alone or in combination) of somatostatin-14, carbachol, vasoactive intestinal peptide (VIP), and prostaglandin E2 (PGE2). In homogenates of duodenal enterocytes, the effect of these agents on adenylate cyclase activity was studied. Basal duodenal HCO3- secretion (3.5 +/- 0.2 mumol/cm/10 min) was reduced dose dependently by somatostatin-14 (10(-11) mol/kg, 10(-9) mol/kg, and 10(-7) mol/kg). Carbachol, VIP, and PGE2 (all 10(-8) mol/kg) increased basal duodenal HCO3- secretion two- to threefold. Somatostatin-14 (10(-7) mol/kg) abolished the stimulatory effect of carbachol and VIP, but not that of PGE2. Basal adenylate cyclase activity in isolated duodenal enterocytes (9.4 +/- 1.0 pmol cAMP/mg protein/min) was unaltered by somatostatin (10(-6) mol/liter) or carbachol (10(-3) mol/liter). VIP (10(-8) mol/liter) and PGE2 (10(-7) mol/liter) increased adenylate cyclase activity two- to threefold, and these effects were unchanged by somatostatin-14 (10(-6) mol/liter). In conclusion, somatostatin-14 inhibits basal and carbachol- and VIP-stimulated duodenal HCO3- secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.

Demographic data from a hospital case series of endoscopically-diagnosed benign peptic ulcer in southern Israel, 1989-1990.

BACKGROUND: A knowledge of the clinical and epidemiological features of duodenal and gastric ulcer is of importance to clinicians and other health care providers. These aspects of ulcer disease have not been studied previously in the Negev region of southern Israel, which is home to 300,000 Jews and 60,000 Bedouin Arabs. METHODS: Clinical, demographic and risk factors were analyzed in a case series of benign duodenal and gastric ulcers (first or recurrent attack) diagnosed at endoscopy at the Soroka Medical Center in the years 1989-1990. RESULTS: There were 336 cases of duodenal ulcer (321 cases in Jews, 15 in Bedouins) and 79 cases of gastric ulcer (all in Jews). The annual rate of endoscopically-detected duodenal ulcer was 54/10(5) in Jews and 13/10(5) in Bedouins. The annual ratio of endoscopically-detected gastric ulcer in Jews was 13/10(5). The ratio of male to female patients was 2.7 for duodenal ulcer in Jews and Bedouins, and 1.9 for gastric ulcer in Jews. The mean age +/- standard deviation at diagnosis was 48 +/- 17 years for duodenal ulcer and 63 +/- 15 years for gastric ulcer (p < 0.001). Duodenal ulcer was significantly commoner than gastric ulcer at all ages, but the ratio DU:GU decreased with increasing age, so that by age 48 years, 20% of all endoscopically-diagnosed ulcers were GU. Of several risk factors examined, smoking was associated with duodenal ulcer (p < 0.05) but not gastric ulcer. Occupation was not a risk factor. Duodenal ulcer was 1.3 times more frequent in winter than summer. CONCLUSIONS: Endoscopically-diagnosed duodenal and gastric ulcer is commoner in Jews than Bedouins and in men than women. Duodenal ulcer is commoner than gastric ulcer and presents at a younger age. Smoking is a risk factor for duodenal ulcer, and European and American ethnic origin is a risk factor for duodenal and gastric ulcers. Bleeding is associated with one-third of endoscopically-diagnosed ulcers in this institution.

Epidemiology of Crohn's disease in southern Israel.

OBJECTIVES: Crohn's disease in Israel was described in the past as being of low incidence, more common in Europe-America-born Jews than other Jews, and of uncharacteristically low morbidity. However, recent experience has suggested that these premises are no longer correct. METHODS: The records of all hospital and outpatient cases of Crohn's disease in southern Israel for the period 1968-1992 were reviewed. Private family practitioners and specialists were contacted to assure complete case ascertainment. RESULTS: The prevalence rate of Crohn's disease among Jews on December 31, 1992, was 50.6/10(5) (Asia-Africa-born Jews 55.0/10(5), Europe-America-born Jews 58.7/10(5), and the rate was 8.2/10(5) among Bedouin Arabs. The annual incidence rate (1987-1992) was calculated as 4.2/10(5)/yr in Jews (Asia-Africa-born 4.6/10(5)/yr, Europe-America-born 3.9/10(5)/yr). The age of presentation declined progressively over the study period, was lower in Israel-born patients than immigrants, and was lower in ileocolonic versus other sites of disease. CONCLUSIONS: The data show that Crohn's disease has become more common in Jews in Israel, losing ethnic differences of frequency, and that it occurs at a younger age than before. In Arabs, the disease is more rare.