Rogier J. De Ridder

Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention

BACKGROUND In everyday practice, the use of colonoscopy for the prevention of colorectal cancer (CRC) is less effective in the proximal than the distal colon. A potential explanation for this is that proximal neoplasms have a more subtle endoscopic appearance, making them more likely to be overlooked. OBJECTIVE To investigate the differences in endoscopic appearance, ie, diminutive size and nonpolypoid shape, of proximal compared with distal colorectal neoplasms. DESIGN Cross-sectional, single-center study. SETTING Endoscopists at the Maastricht University Medical Center in the Netherlands who were previously trained in the detection and classification of nonpolypoid colorectal lesions. PATIENTS Consecutive patients undergoing elective colonoscopy. MAIN OUTCOME MEASUREMENTS Endoscopic appearance, ie, diminutive size (<6 mm) or nonpolypoid shape (height less than half of the diameter) of colorectal adenomas and serrated polyps (SPs), with a focus on adenomas with advanced histology, ie, high-grade dysplasia or early CRC and SPs with dysplasia or large size. RESULTS We included 3720 consecutive patients with 2106 adenomas and 941 SPs. We found that in both men and women, proximal adenomas with high-grade dysplasia/early CRC (n = 181) were more likely to be diminutive or nonpolypoid than distal ones (76.3% vs 26.2%; odds ratio [OR] 9.24; 95% CI, 4.45-19.2; P < .001). Of the proximal adenomas, 84.4% were diminutive or nonpolypoid compared with 68.0% of the distal ones (OR 2.66; 95% CI, 2.14-3.29; P < .001). Likewise, large/dysplastic SPs in the proximal colon were more often nonpolypoid than distal ones (66.2% vs 27.8%; OR 5.51; 95% CI, 2.79-10.9; P < .001). LIMITATIONS Inclusion of both symptomatic and asymptomatic patients. CONCLUSIONS Proximal colorectal neoplasms with advanced histology frequently are small or have a nonpolypoid appearance. These findings support careful inspection of the proximal colon, if quality of cancer prevention with the use of colonoscopy is to be optimized.

Endoscopic characterization of sessile serrated adenomas/polyps with and without dysplasia.

BACKGROUND AND STUDY AIMS Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colorectal cancer (CRC), but their endoscopic detection can be difficult. We therefore examined the endoscopic characteristics of SSA/Ps with and without dysplasia in a cross-sectional study. PATIENTS AND METHODS We reviewed clinical, endoscopic, and histopathologic data from patients undergoing colonoscopy between February 2008 and February 2012. We categorized colorectal polyps according to anatomic site, size, and shape, and classified serrated polyps using the World Health Organization (WHO) classification. Multiple logistic regression analyses examined potential differences regarding site, size, and shape between SSA/Ps and colorectal adenomas (overall and advanced only). RESULTS We examined 7433 patients (mean age 59 years, 45.9 % men) with 5968 colorectal polyps. In total, we found 170 SSA/Ps (170/5968, 2.9 %), including 63 SSA/Ps with dysplasia (1.1 %) and 107 SSA/Ps without dysplasia (1.8 %). Compared with SSA/Ps with dysplasia, SSA/Ps without dysplasia were more often proximally located (odds ratio [OR] 3.3, 95 % confidence interval [95 %CI] 1.7 - 6.4), but less often < 6 mm in size (OR 0.6, 95 %CI 0.3 - 1.1). No significant differences were found regarding location between SSA/Ps with dysplasia and advanced adenomas (proximal colon, 47.6 % vs. 40.1 %). However, SSA/Ps with dysplasia were more often < 6 mm in size than advanced adenomas (OR 0.3, 95 %CI 0.2 - 0.5). Of the 63 dysplastic SSA/Ps, 6 (9.5 %) contained high grade dysplasia, but none invasive carcinoma. CONCLUSIONS SSA/Ps with dysplasia are frequently < 6 mm in size, located throughout the colon and 9.5 % of them contain high grade dysplasia. These findings underscore the importance of high quality colonoscopic examination to maximize protection against CRC.

Chronic radiation proctitis: tricks to prevent and treat.

ObjectiveThe purpose of this study was to give an overview of the measures used to prevent chronic radiation proctitis (CRP) and to provide an algorithm for the treatment of CRP.MethodsMedical literature databases including PubMed and Medline were screened and critically analyzed for relevance in the scope of our purpose.ResultsCRP is a relatively frequent late side effect (5–20%) and mainly dependent on the dose and volume of irradiated rectum. Radiation treatment (RT) techniques to prevent CRP are constantly improving thanks to image-guided RT and intensity-modulated RT. Also, newer techniques like protons and new devices such as rectum spacers and balloons have been developed to spare rectal structures. Biopsies do not contribute to diagnosing CRP and should be avoided because of the risk of severe rectal wall damage, such as necrosis and fistulas. There is no consensus on the optimal treatment of CRP. A variety of possibilities is available and includes topical and oral agents, hyperbaric oxygen therapy, and endoscopic interventions.ConclusionsCRP has a natural history of improving over time, even without treatment. This is important to take into account when considering these treatments: first be conservative (topical and oral agents) and be aware that invasive treatments can be very toxic.

Optical diagnosis of colorectal polyps using high-definition i-scan: An educational experience

AIM To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS We used a digital library of HD i-scan still images, comprising twin pictures (surface enhancement and tone enhancement), collected at our university hospital. We defined endoscopic features of adenomatous and non-adenomatous polyps, according to the following parameters: color, surface pattern and vascular pattern. We familiarized the participating endoscopists on optical diagnosis of colorectal polyps using a 20-min didactic training session. All endoscopists were asked to evaluate an image set of 50 colorectal polyps with regard to polyp histology. We classified the diagnoses into high confidence (i.e., cases in which the endoscopist could assign a diagnosis with certainty) and low confidence diagnoses (i.e., cases in which the endoscopist preferred to send the polyp for formal histology). Mean sensitivity, specificity and accuracy per endoscopist/image were computed and differences between groups tested using independent-samples t tests. High vs low confidence diagnoses were compared using the paired-samples t test. RESULTS Eleven endoscopists without previous experience on optical diagnosis evaluated a total of 550 images (396 adenomatous, 154 non-adenomatous). Mean sensitivity, specificity and accuracy for diagnosing adenomas were 79.3%, 85.7% and 81.1%, respectively. No significant differences were found between gastroenterologists and trainees regarding performances of optical diagnosis (mean accuracy 78.0% vs 82.9%, P = 0.098). Diminutive lesions were predicted with a lower mean accuracy as compared to non-diminutive lesions (74.2% vs 93.1%, P = 0.008). A total of 446 (81.1%) diagnoses were made with high confidence. High confidence diagnoses corresponded to a significantly higher mean accuracy than low confidence diagnoses (84.0% vs 64.3%, P = 0.008). A total of 319 (58.0%) images were evaluated as having excellent quality. Considering excellent quality images in conjunction with high confidence diagnosis, overall accuracy increased to 92.8%. CONCLUSION After a single training session, endoscopists with varying levels of experience can already provide optical diagnosis with an accuracy of 84.0%.

Intraduodenal administration of intact pea protein effectively reduces food intake in both lean and obese male subjects.

Background Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects. Methods Ten lean (BMI:23.0±0.7 kg/m2) and ten obese (BMI:33.4±1.4 kg/m2) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded. Results CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA. Conclusions Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity.

Comparing quality, safety, and costs of colonoscopies performed by nurse vs physician trainees

BACKGROUND & AIMS We evaluated the quality and safety of colonoscopies performed by nurse and physician endoscopy trainees as well as the cost differences. METHODS We performed a study of 7 nurse and 8 physician (gastroenterology fellows) endoscopy trainees at 2 medical centers in the Netherlands from September 2008 through April 2012. At the beginning of the study, the subjects had no experience in endoscopy; they were trained in gastrointestinal endoscopy according to the regulations of the Dutch Society of Gastroenterology, performing a minimum of 100 colonoscopies. Each trainee then performed 135 consecutive colonoscopies (866 total by nurse trainees and 1080 by physician trainees) under supervision of a gastroenterologist; the colonoscopies were evaluated for quality and safety. We performed statistical analyses of data, assessing multilevel and cost minimization. The mean age of the patients was 57 years, and about half were women in each group. RESULTS The endoscopic quality and safety were comparable between nurse and physician trainees. Overall rates of cecal intubation were 95% for nurses and 93% for physicians (P = .38), including procedures that required assistance from a supervisor; mean withdrawal times were 10.4 and 9.8 minutes, respectively (P = .44). Each group detected 27% of adenomas and had a 0.5% rate of complication. In both groups, the rates of unassisted cecal intubation gradually increased with the number of colonoscopies performed, from 70% for nurses and 74% for physicians at the beginning to 89% and 86%, respectively, at the end of the assessment period. Using a strategy in which 1 gastroenterologist supervises 3 nurses, the personnel costs decreased from

An acute intake of plant stanol esters alters immune-related pathways in the jejunum of healthy volunteers

64.65 to

Validation of ussing chamber technology to study satiety hormone release from human duodenal specimens.

54.58. CONCLUSIONS In a supervised setting, nurse endoscopists perform colonoscopies according to quality and safety standards that are comparable with those of physician endoscopist and can substantially reduce costs.

Endoscopic versus percutaneous biliary drainage in patients with resectable perihilar cholangiocarcinoma: a multicentre, randomised controlled trial

Plant sterols and stanols inhibit intestinal cholesterol absorption and consequently lower serum LDL-cholesterol (LDL-C) concentrations. The underlying mechanisms are not yet known. In vitro and animal studies have suggested that changes in intestinal sterol metabolism are attributed to the LDL-C-lowering effects of plant stanol esters. However, similar studies in human subjects are lacking. Therefore, we examined the effects of an acute intake of plant stanol esters on gene expression profiles of the upper small intestine in healthy volunteers. In a double-blind cross-over design, fourteen healthy subjects (eight female and six male; age 21-55 years), with a BMI ranging from 21 to 29 kg/m², received in random order a shake with or without plant stanol esters (4 g). At 5 h after consumption of the shake, biopsies were taken from the duodenum (around the papilla of Vater) and from the jejunum (20 cm distal from the papilla of Vater). Microarray analysis showed that the expression profiles of genes involved in sterol metabolism were not altered. Surprisingly, the pathways involved in T-cell functions were down-regulated in the jejunum. Furthermore, immunohistochemical analysis showed that the number of CD3 (cluster of differentiation number 3), CD4 (cluster of differentiation number 4) and Foxp3⁺ (forkhead box P3-positive) cells was reduced in the plant stanol ester condition compared with the control condition, which is in line with the microarray data. The physiological and functional consequences of the plant stanol ester-induced reduction of intestinal T-cell-based immune activity in healthy subjects deserve further investigation.

The acute effects on duodenal gene expression in healthy men following consumption of a low-fat meal enriched with theobromine or fat

By developing novel screening technologies to test effects of food ingredients on hormone release, which are comparable to the in vivo situation, fewer tests may have to be performed using volunteers, whereas it still provides information that can be extrapolated to the human situation. In an in vivo intervention study, 10 lean (BMI: 20–25 kg/m2) and 10 obese (BMI >30 kg/m2) were recruited. All subjects randomly received pea protein (PP) solutions or placebo, orally and intraduodenally. Cholecystokinin (CCK) and glucagon like peptide 1 (GLP‐1) release was measured over 2 h. During the oral interventions, gastrointestinal (GI) fluids were retrieved. For the present ex vivo study, duodenal biopsies were taken and placed in Ussing chambers. The luminal side was exposed to PP, placebo, intraduodenal fluid after oral PP‐intake and oral placebo–intake in vivo, and a commercial pea‐hydrolysate for 2 h. CCK and GLP‐1 levels were measured at the serosal side. After intraduodenal PP administration in vivo, the area under the curve (AUC) for both CCK and GLP‐1 was significantly increased in both lean and obese subjects. In the ex vivo study, exposure to PP resulted in significantly elevated levels of CCK and GLP‐1 compared to all other test solutions. These results indicate that the ex vivo Ussing chamber technology is a valid alternative for in vivo studies, and may therefore serve as a suitable screening tool for studying the effects of nutritional compounds on the release of satiety hormones.