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C D Johnson

Publications and source records attributed to C D Johnson.

At least 37 records · Page 2Linked to original sources

Non-compliance with national guidelines in the management of acute pancreatitis in the United kingdom.

BACKGROUND: Deficiencies and lack of standardisation of the management of acute pancreatitis in the UK have been reported. National UK guidelines for the management of acute pancreatitis were published in 1998. However, implementation of national guidelines in other areas has been patchy, suggesting that evaluation of the uptake of the pancreatitis guidelines would be appropriate. AIM: Identification of current practice in the management of acute pancreatitis as reported by consultant surgeons, in order to determine how effectively the UK guidelines have been introduced into practice. METHODS: A questionnaire was posted to 1,072 full members of the Association of Surgeons of Great Britain and Ireland. It consisted of 13 questions that aimed to identify the surgeon's practice in the management of patients with acute pancreatitis in relation to key points in the UK guidelines. We compared the practice of hepatobiliary and pancreatic (HBP) vs. non-HBP specialists, and teaching vs. non-teaching hospital surgeons using the chi(2) test. RESULTS: Of 538 responses (50%), 519 were from consultant surgeons. 59 did not look after patients with acute pancreatitis and 89 (17%) had a HBP interest. There were differences between the recommendations in the guidelines and reported practice, particularly in the use of critical care resources and referral to specialist units. Of consultants looking after acute pancreatitis 371 (72%) were non-HBP specialists. There were significant overall differences between the practice of HBP specialists and non-specialists: in severity assessment (Glasgow and C-reactive protein vs. Ranson criteria); indication and timing of requesting computed tomography (routinely at 7-10 days vs. when clinically indicated); nutritional support (enteral feeding vs. no support), and in common bile duct assessment prior to cholecystectomy (intra-operative cholangiography vs. endoscopic retrograde cholangiopancreatography). There was no significant difference between practice in teaching and non-teaching hospitals. CONCLUSION: Implementation of national guidelines for the management of acute pancreatitis was greater in the practice of HBP specialists than non-specialists. This has implications for the rationale of creating guidelines, and for the strategies associated with their introduction.

Acute Disease↗

Deficiencies of micronutrients, altered bowel function, and quality of life during late follow-up after pancreaticoduodenectomy for malignancy.

BACKGROUND/AIM: A previous study in our unit showed an inadequate dietary intake of fat-soluble vitamins and energy after pancreaticoduodenectomy (PD). This study was designed to determine whether deficiencies in dietary intake of micronutrients lead to nutritional deficiencies and to examine the impact of dietary advice on nutrition, bowel function, and quality of life. METHODS: Ten patients who had undergone PD for malignant disease more than 6 months previously were studied at baseline and follow-up 8 weeks apart. Dietary intakes of energy, fat, and micronutrients were assessed by analysis of weighed food diaries, and serum vitamins and trace elements were measured at each visit. Quality of life questionnaires (EORTC QLQ30 and PAN 26) were answered, and a clinical assessment of the bowel function was made. Targeted dietary intervention was given, where indicated, and its impact on the study parameters was assessed at the second clinic visit. RESULTS: The patients were generally well nourished. Dietary deficiencies of fat-soluble vitamins were detected (vitamin A, n = 2; vitamin D, n = 10; vitamin E, n = 2), but these correlated with serum deficiency only for vitamin A. The selenium intake was borderline or insufficient in 6 patients' diet, with serum deficiencies in 4. Despite normal intakes of iron and zinc, half the patients showed serum deficiency. The bowel function was an important factor in quality of life, and symptoms improved in 3 patients with enzyme supplements and antidiarrhoeal medication. CONCLUSIONS: PD patients appear to be prone to a predictable set of micronutrient deficiencies that may be compounded by insufficient dietary intake. The bowel function is important to these patients, and it should be optimized with aggressive enzyme replacement. Dietary intervention appears to make little short-term impact in the areas studied.

Aged↗

A phase II trial of marimastat in advanced pancreatic cancer.

Pancreatic cancer has a poor response to conventional chemotherapy and radiotherapy. Inhibition of matrix metalloproteinase activity involved in tumour invasion and metastases is a novel biological approach for cancer treatment. This multicentre phase II clinical trial assessed marimastat, an oral matrix metalloproteinase inhibitor, in patients with advanced pancreatic cancer. A total of 113 patients received marimastat for 28 days at 100 mg b.d. (n = 9), 25 mg o.d. (n = 90) or 10 mg b.d. (n = 14). Patients with a response to treatment could continue marimastat beyond 28 days. Of 113 patients, 90 (80%) completed the 28-day study and 83 (73%) continued treatment. The principal side effect was arthralgia in 14 (12%) patients at 28 days and 33 (29%) patients over the whole study. There were 31 patients (27%) who required dose modification. Of 76 patients with evaluable CA19-9 levels, 23 (30%) showed no increase or fall in CA19-9. Of 83 patients with radiologically assessable disease, 41 (49%) had stable disease. The median survival was 245 days for those with a stable or falling CA19-9 level 128 days in those with rising CA19-9. The overall survival was 3.8 months. 5.9 months for stage II, 4.7 months for stage III and 3 months for stage IV disease. Of 90 patients, 46 (51%) had stabilization or reduction in pain, mobility and analgesia scores. Further development and clinical evaluation of matrix metalloproteinase inhibitors for the treatment of pancreatic cancer is warranted.

Adenocarcinoma↗

A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans.

BACKGROUND: Both animals and plants respond rapidly to pathogens by inducing the expression of defense-related genes. Whether such an inducible system of innate immunity is present in the model nematode Caenorhabditis elegans is currently an open question. Among conserved signaling pathways important for innate immunity, the Toll pathway is the best characterized. In Drosophila, this pathway also has an essential developmental role. C. elegans possesses structural homologs of components of this pathway, and this observation raises the possibility that a Toll pathway might also function in nematodes to trigger defense mechanisms or to control development. RESULTS: We have generated and characterized deletion mutants for four genes supposed to function in a nematode Toll signaling pathway. These genes are tol-1, trf-1, pik-1, and ikb-1 and are homologous to the Drosophila melanogaster Toll, dTraf, pelle, and cactus genes, respectively. Of these four genes, only tol-1 is required for nematode development. None of them are important for the resistance of C. elegans to a number of pathogens. On the other hand, C. elegans is capable of distinguishing different bacterial species and has a tendency to avoid certain pathogens, including Serratia marcescens. The tol-1 mutants are defective in their avoidance of pathogenic S. marcescens, although other chemosensory behaviors are wild type. CONCLUSIONS: In C. elegans, tol-1 is important for development and pathogen recognition, as is Toll in Drosophila, but remarkably for the latter rôle, it functions in the context of a behavioral mechanism that keeps worms away from potential danger.

Actinomycetales↗

Lack of enteral feeding increases expression of E-selectin after LPS challenge.

BACKGROUND: Total parenteral nutrition (IV-TPN) increases neutrophil accumulation in the small intestine, expression of intestinal ICAM-1 and P-selectin, and upregulates E-selectin expression in the lung. Endothelial activation induced by lack of enteral nutrition may change the response to injury or infection. This study investigated whether nutrition influenced the expression of the adhesion molecule, E-selectin and ICAM-1, following endotoxin challenge. MATERIALS AND METHODS: Forty-three mice were injected with saline, 2, 20, 200, 2000, or 10000 microg/kg lipopolysaccharide (LPS) intraperitoneally. E-selectin expression in the lung, small intestine, and heart was quantified at 3 h after challenge, while ICAM-1 was measured at 5 h, using the dual-radiolabeled monoclonal antibody technique. Next, 80 mice were fed chow, intragastric (IG)-TPN, or IV-TPN for 5 days, and then received intraperitoneal 2 or 200 microg/kg LPS. E-selectin and ICAM-1 expression in organs was measured at 3 and 5 h after endotoxin, respectively. RESULTS: E-selectin expression in organs increased LPS dose dependently. ICAM-1 levels reached early peaks in the lung and in the intestine. Also, IV-TPN significantly increased E-selectin expression in the small intestine and tended to increase pulmonary E-selectin, when compared to chow or IG-TPN animals. There were no significant differences in E-selectin expression among three diet groups after 200 microg/kg LPS challenge. No differences in ICAM-1 expression were observed in any organ among the three groups after 2 or 200 microg/kg LPS injection. CONCLUSIONS: E-selectin rather than ICAM-1, because of the expression pattern after various dosages of LPS challenge, may be a determining factor for the degree of LPS-induced inflammation at the early phase. Lack of enteral nutrition may increase inflammatory response through enhanced gut E-selectin levels after a small dose of LPS.

Animals↗

Impairment of mucosal immunity by total parenteral nutrition: requirement for IgA in murine nasotracheal anti-influenza immunity.

Secretory IgA (SIgA) is the primary mucosal Ig and has been shown to mediate nasotracheal (NT) mucosal immunity in normal immune BALB/c mice. This finding has been challenged by a report of NT immunity without IgA in knockout mice, suggesting that IgA may not be necessary for the protection of mucosal surfaces. Although other protective mechanisms may become active in the congenital absence of SIgA, these mechanisms are not the primary means of protection in normal mice. In this paper we show that feeding chemically defined total parenteral nutrition (TPN) to genetically normal, immune ICR mice by the i.v. route results in loss of nasal anti-influenza immunity and a significant drop in influenza-specific SIgA in the upper respiratory tract compared with chow-fed mice (p < 0.005), while the serum influenza-specific IgG titer is unaffected. Loss of upper respiratory tract mucosal immunity is not related to serum Ab, because 10 of 13 TPN-fed mice shed virus into their nasal secretions despite adequate serum anti-influenza IgG titers. The number of IgG Ab-secreting cells in the nasal passages and spleens of TPN-fed mice was unaffected, while both the number and the percentage of splenic IgA-secreting cells were decreased relative to those in chow-fed animals. The loss of immunity is due to the route of nutrition, not the composition of the diet, because TPN solution fed orally via gastrostomy instead of i.v. maintains NT anti-influenza mucosal immunity. We hypothesize that delivery of nutrition via the gut triggers the release of gastrointestinal neuropeptides necessary for maintenance of the mucosal immune system.

Administration, Intranasal↗

Development of an EORTC disease-specific quality of life module for use in patients with gastric cancer.

Quality of life (QL) is an important outcome in clinical trials in oncology. There is currently no valid international QL measure for gastric cancer. This paper describes the development of a QL module for gastric cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ-C30) questionnaire. Phases I to III of module development were conducted in the United Kingdom, France, Germany and Spain according to EORTC QL Group guidelines. Twenty relevant QL issues were generated from the literature and interviews with health professionals (n=24) and patients (n=58). This produced a 24 item provisional module. Further testing in 115 patients resulted in the QLQ-STO22, containing 22 questions, conceptualised into five scales and four single items, related to disease symptoms, treatment side-effects and emotional issues specific to gastric cancer. The use of the QLQ-C30 supplemented by the QLQ-STO22 will provide a comprehensive QL measure for international trials in gastric cancer.

Adult↗

Randomized, dose-finding phase III study of lithium gamolenate in patients with advanced pancreatic adenocarcinoma.

BACKGROUND: Chemotherapy for pancreatic cancer offers small survival benefits and considerable side-effects. Unsaturated fatty acids have an antitumour effect in experimental studies; in phase II studies few side-effects were seen. METHODS: In this group-sequential, open-label, randomized study, 278 patients with a diagnosis of inoperable pancreatic cancer were treated with either oral (700 mg daily for 15 days), low-dose (0.28 g/kg) or high-dose (0.84 g/kg) intravenous lithium gamolenate (LiGLA). The primary endpoint was survival time from randomization using Kaplan-Meier estimates. RESULTS: Median survival after oral and low-dose intravenous treatment was 129 and 121 days respectively. Median survival after high-dose intravenous treatment was 94 days. A good Karnofsky score and the absence of metastases were associated with increased survival. Haemolysis, a marker of rapid infusion, was associated with a median survival time of 249 days in the low-dose intravenous group. CONCLUSION: Oral or low-dose intravenous LiGLA led to survival times similar to those of other treatments for pancreatic cancer although one subgroup (low-dose intravenous LiGLA with haemolysis) had longer survival. High-dose intravenous treatment appeared to have an adverse effect. Systemic treatment with LiGLA cannot be recommended for the treatment of pancreatic cancer.

Adenocarcinoma↗

Haemobilia.

BACKGROUND: This review aims to establish whether increased use of invasive procedures and the trend toward conservative management of major trauma has resulted in an increased incidence of haemobilia. METHOD: A Medline (http://igm.nlm.nih.gov/)-based search of the English language literature from January 1996 to December 1999 inclusive was performed using the keywords haemobilia, hemobilia, haematobilia and hematobilia. The presentation, aetiology, investigation, management and outcome of 222 cases were reviewed. RESULTS: Two-thirds of cases were iatrogenic while accidental trauma accounted for 5 per cent. Haemobilia may be major, constituting life-threatening haemorrhage, or minor; it may present many weeks after the initial injury. Diagnosis is most commonly confirmed by angiography. Management is aimed at stopping bleeding and relieving biliary obstruction; 43 per cent of cases were managed conservatively and 36 per cent were managed by transarterial embolization (TAE). Surgery was indicated when laparotomy was performed for other reasons and for failed TAE. The mortality rate was 5 per cent. CONCLUSIONS: Although the incidence of iatrogenic haemobilia has risen considerably, the bleeding is often minor and can be managed conservatively. When more urgent intervention is required, TAE is usually the treatment of choice. There is no evidence that the conservative management of accidental liver trauma increases the risk of haemobilia.

Hemobilia↗

Isometric back extension endurance tests: a review of the literature.

OBJECTIVE: To review the literature that describes and evaluates the use of isometric back extension endurance tests. DATA COLLECTION: Relevant articles in English were retrieved through a search of MEDLINE and the Index to Chiropractic Literature. Key search terms were back muscle endurance, isometric back endurance, trunk extensors, back muscle performance, and Sorensen test. DATA SYNTHESIS: The principal criterion for inclusion was as follows: any study that discussed or tested an isometric type of back endurance extension test. Studies that were excluded did not use an isometric testing protocol. Thirty-seven of the initial studies are included in this review. RESULTS: Six different types of isometric back extension endurance testing methods were found. Three of these procedures require special testing devices. Much of the research on this topic has centered on a procedure known as the Sorensen test. Normative databases have been established for the Sorensen test and 2 other test types. Validity and reliability have been assessed for some of the procedures. CONCLUSIONS: The influence of motivation and effort exerted by the subject are limiting factors in all of the tests reviewed. These psychologic factors warrant further research. On the basis of the literature reviewed, we determined that the Sorensen is probably the most clinically useful of these tests; it is easy to perform, requires no special equipment, and enjoys the most support from the literature.

Adult↗

Enteral nutrition prevents remote organ injury and death after a gut ischemic insult.

OBJECTIVE: To determine whether parenteral feeding (IV-TPN) influences the local and systemic response to an intestinal insult. SUMMARY BACKGROUND DATA: Parenteral feeding increases ICAM-1 expression and attracts neutrophils (PMNs) to the intestine compared with enterally fed animals. Because the gut is a priming bed for PMNs, the authors hypothesized that IV-TPN may affect organ injury after gut ischemia-reperfusion (I/R). METHODS: Mice were randomized to chow, IV-TPN, intragastric TPN, or complex enteral diet for 5 days' feeding. In experiment 1, 162 mice underwent 15 or 30 minutes of gut I/R, and death was recorded at 72 hours. In experiment 2, 43 mice underwent 15 minutes of gut ischemia and permeability was measured by 125I-labeled albumin at 3 hours after reperfusion. Lung PMN accumulation was measured by myeloperoxidase assay. In experiment 3, albumin leak was tested in the complex enteral diet group (n = 5) and the intragastric TPN group (n = 5) after 30 minutes of gut ischemia and 1 hour of reperfusion. RESULTS: In experiment 1, enteral feeding significantly reduced the death rate compared with IV-TPN after 15 minutes of I/R. After 30 minutes of gut ischemia, the IV-TPN and intragastric TPN groups showed a higher death rate than the chow and enteral diet groups. In experiment 2, IV-TPN significantly increased pulmonary and hepatic 125I albumin leak compared with enteral feeding without increasing pulmonary myeloperoxidase levels. In experiment 3, there were no differences in 125I albumin leak between the complex enteral diet and intragastric TPN groups. CONCLUSION: Enteral feeding reduced the death rate and organ permeability after 15 minutes of ischemia. However, prolonged ischemia (30 minutes) eliminated any benefits of intragastric TPN on survival.

Animals↗

Modulation of organ ICAM-1 expression during IV-TPN with glutamine and bombesin.

The gut primes neutrophils (PMNs) during injury, which can then induce distant organ damage after a second insult. ICAM-1 is an important adhesion molecule in PMN attachment to the vascular endothelium. Parenteral nutrition (TPN) decreases gut levels of interleukin (IL)-4 and IL-10, two cytokines that are normal inhibitors of ICAM-1 expression. TPN also increases gut ICAM-1 expression and PMN accumulation. Since glutamine (GLN) and bombesin (BBS) prevent TPN-associated impairment of mucosal immunity, we hypothesized that GLN and BBS would modulate organ ICAM-1 expression in association with normalization of IL-4 and IL-10 levels. Forty-four mice were fed chow, TPN, or GLN-TPN (isonitrogenous 2% GLN-enriched TPN). After 5 days of diets, ICAM-1 expression was quantified in organs using the dual radiolabeled monoclonal antibody technique. In the next experiment, 29 mice were fed chow, TPN, or BBS-TPN (BBS 15 microg/kg TID) for 5 days to measure organ ICAM-1 expression. Total IL-4 and IL-10 levels were measured with ELISA from intestinal homogenates of another set of 52 mice fed chow, TPN, GLN-TPN, or BBS-TPN. TPN significantly increased ICAM-1 expression in the lung, kidney, and intestine compared with chow mice. GLN-TPN decreased intestinal, but not lung, ICAM-1 expression, while BBS-TPN reduced pulmonary, but not gut, ICAM-1 levels. GLN- and BBS-TPN returned gut IL-4 levels to normal, but failed to increase IL-10 levels. GLN and BBS had different effects on organ ICAM-1 expression induced by lack of enteral nutrition. Mechanisms other than recovery of IL-4 alone may be responsible for gut ICAM-1 expression.

Animals↗

Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis.

BACKGROUND: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate. FINDINGS: Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups. INTERPRETATION: The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis

Acute Disease↗

Automated polyp detection at CT colonography: feasibility assessment in a human population.

PURPOSE: To test the feasibility of and improve a computer algorithm to automatically detect colonic polyps in real human computed tomographic (CT) colonographic data sets. MATERIALS AND METHODS: Twenty patients with known polyps underwent CT colonography in the supine position. CT colonographic data were processed by using a shape-based algorithm that depicts masses that protrude into the lumen. We studied nine shape criteria and three isosurface threshold settings. Results were compared with those of conventional colonoscopy performed the same day. RESULTS: There were 50 polyps (28 were > or =10 mm in size; 12, 5-9 mm; 10, <5 mm). The sensitivity with optimal settings for detecting polyps 10 mm or greater was 64% (18 of 28). Sensitivity improved to 71% (10 of 14) for polyps 10 mm or greater in well-distended colonic segments. Performance decreased for polyps less than 10 mm, poorly distended colonic segments, and other shape algorithms. There was a mean of six false-positive lesion sites per colon. These sites were reduced 39% to 3.5 per colon by sampling CT attenuation at the lesion site and discarding sites having attenuation less than a threshold. CONCLUSION: Automated detection of colonic polyps, especially clinically important large polyps, is feasible. Colonic distention is an important determinant of sensitivity. Further increases in sensitivity may be achieved by adding prone CT colonography.

Adult↗

CT colonography: single- versus multi-detector row imaging.

PURPOSE: To compare respiratory artifacts, colonic distention, and polyp detection at computed tomographic (CT) colonography by using single- and multi-detector row helical CT systems. MATERIALS AND METHODS: A total of 237 consecutive patients received subcutaneously administered glucagon and underwent prone and supine CT colonography with single-detector row CT (n = 77) and multi-detector row CT (n = 160), followed by colonoscopy. Examination results were graded for colonic distention, respiratory artifacts, and polyp depiction by two radiologists working independently. RESULTS: Suboptimal colonic distention was significantly more common with single-detector row CT and was present in at least one segment in 52% (40 of 77 patients) of examinations versus only 19% (30 of 160 patients) with multi-detector row CT (P <.001). Mild respiratory artifacts were present in 61% (47 of 77 patients) of single-detector row CT examinations versus only 16% (26 of 160 patients) of multi-detector row CT examinations (P <.001). Depiction of polyps larger than 10 mm was 89% (eight of nine polyps) for single-detector row CT and 80% (eight of 10 polyps) for multi-detector row CT (P >.05). CONCLUSION: CT colonography performed with multi-detector row CT significantly improved the demonstration of colonic distention and depicted fewer respiratory artifacts compared with single-detector row CT. No significant differences in the depiction of polyps larger than 10 mm were demonstrated between single- and multi-detector row CT for a small number of polyps. Studies with a larger prevalence of clinically important polyps are needed for further evaluation of differences in polyp detection.

Adult↗

CT colonography without cathartic preparation: feasibility study.

PURPOSE: To evaluate methods for contrast material labeling of stool in the unprepared colon for computed tomographic (CT) colonography and to determine their sensitivity for polyp detection. MATERIALS AND METHODS: Fifty-six patients with suspected or known polyps were assigned to five groups. Two to seven doses of 225 mL of dilute contrast material were orally administered during 24 or 48 hours. Transverse CT images were assessed for effectiveness of stool labeling. Colonoscopy was performed in all patients and was the standard. Two radiologists blinded to prior imaging and colonoscopic results assessed polyp detection. RESULTS: For each group, average stool labeling scores and ranges were as follows: 24 hour two dose, 16% and 8%-21%; 24 hour five dose, 53% and 27%-66%; 48 hour four dose, 38% and 22%-48%; 48 hour six dose, 68% and 54%-77%; and 48 hour seven dose, 88% and 75%-98%. Sensitivity for the two radiologists for the identification of patients with polyps 1 cm or larger for each group was as follows: 24 hour two dose, 50% and 67%; 24 hour five dose, 100% and 100%; 48 hour four dose, 58% and 75%; 48 hour six dose, 56% and 67%; and 48 hour seven dose, 100% and 80%. CONCLUSION: Ingestion of contrast material adequately labels stool for lesion identification; a 48-hour lead time and multiple doses of contrast material are required. Sensitivity for polyp detection in patients with adequate stool labeling approaches the sensitivity for polyp detection in prepared colons.

Barium Sulfate↗