Summary Background Although colonoscopy is the accepted standard for detection of colorectal adenomas and cancers, many adenomas and some cancers are missed. To avoid interval colorectal cancer, the ...adenoma miss rate of colonoscopy needs to be reduced by improvement of colonoscopy technique and imaging capability. We aimed to compare the adenoma miss rates of full-spectrum endoscopy colonoscopy with those of standard forward-viewing colonoscopy. Methods We did an international, multicentre, randomised trial at three sites in Israel, one site in the Netherlands, and two sites in the USA between Feb 1, 2012, and March 31, 2013. Patients aged 18–70 years referred for colorectal cancer screening, polyp surveillance, or diagnostic assessment underwent same-day, back-to-back tandem colonoscopy with standard forward-viewing colonoscope and the full-spectrum endoscopy colonoscope. The patients were randomly assigned (1:1), via computer-generated randomisation with block size of 20, to which procedure was done first. The endoscopist was masked to group allocation until immediately before the start of colonoscopy examinations; patients were not masked. The primary endpoint was adenoma miss rates. We did per-protocol analyses. This trial is registered with ClinicalTrials.gov , number NCT01549535. Findings 197 participants were enrolled. 185 participants were included in the per-protocol analyses: 88 (48%) were randomly assigned to receive standard forward-viewing colonoscopy first, and 97 (52%) to receive full-spectrum endoscopy colonoscopy first. By per-lesion analysis, the adenoma miss rate was significantly lower in patients in the full-spectrum endoscopy group than in those in the standard forward-viewing procedure group: five (7%) of 67 vs 20 (41%) of 49 adenomas were missed (p<0·0001). Standard forward-viewing colonoscopy missed 20 adenomas in 15 patients; of those, three (15%) were advanced adenomas. Full-spectrum endoscopy missed five adenomas in five patients in whom an adenoma had already been detected with first-pass standard forward-viewing colonoscopy; none of these missed adenomas were advanced. One patient was admitted to hospital for colitis detected at colonoscopy, whereas five minor adverse events were reported including vomiting, diarrhoea, cystitis, gastroenteritis, and bleeding. Interpretation Full-spectrum endoscopy represents a technology advancement for colonoscopy and could improve the efficacy of colorectal cancer screening and surveillance. Funding EndoChoice.
Colorectal cancer is a leading cause of death. Colonoscopy is the criterion standard for detection and removal of precancerous lesions and has been shown to reduce mortality. The polyp miss rate ...during colonoscopies is 22% to 28%. DEEP DEtection of Elusive Polyps (DEEP2) is a new polyp detection system based on deep learning that alerts the operator in real time to the presence and location of polyps. The primary outcome was the performance of DEEP2 on the detection of elusive polyps.
The DEEP2 system was trained on 3611 hours of colonoscopy videos derived from 2 sources and was validated on a set comprising 1393 hours from a third unrelated source. Ground truth labeling was provided by offline gastroenterologist annotators who were able to watch the video in slow motion and pause and rewind as required. To assess applicability, stability, and user experience and to obtain some preliminary data on performance in a real-life scenario, a preliminary prospective clinical validation study was performed comprising 100 procedures.
DEEP2 achieved a sensitivity of 97.1% at 4.6 false alarms per video for all polyps and of 88.5% and 84.9% for polyps in the field of view for less than 5 and 2 seconds, respectively. DEEP2 was able to detect polyps not seen by live real-time endoscopists or offline annotators in an average of .22 polyps per sequence. In the clinical validation study, the system detected an average of .89 additional polyps per procedure. No adverse events occurred.
DEEP2 has a high sensitivity for polyp detection and was effective in increasing the detection of polyps both in colonoscopy videos and in real procedures with a low number of false alarms. (Clinical trial registration number: NCT04693078.)
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Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for ...recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020-January 2023. Those with a known familial PV (n = 370) were excluded from the analysis. Among the remainder, 128/1758 (7%) were heterozygous for at least one variant, and 44 (34%) carried a PV of medium-high penetrance (MHPV). Cancer was diagnosed in 1519/1758 patients (86%). The diagnostic yield of founder MHPV testing was 2% in cancer patients and 4% in healthy individuals with a positive family history. It was higher in Ashkenazi Jews than non-Ashkenazi Jews and Arabs, but not over 10% for any type of cancer, and it was significantly higher in younger (<40 years) than older (>50 years) individuals (7% vs. 1%). Eighty-four of the heterozygotes (66%), mostly Ashkenazi Jews, harbored a low-penetrance variant (LPV) not associated with the diagnosed cancer, usually
c.3902T>A. These findings question the advantage of two-step testing. LPVs should not be included in targeted testing because this can lead to an overestimation of the yield, and their detection does not preclude further comprehensive testing.
POT1 (Protection of Telomeres 1) is a key component of the six-membered shelterin complex that plays a critical role in telomere protection and length regulation. Germline variants in the
gene have ...been implicated in predisposition to cancer, primarily to melanoma and chronic lymphocytic leukemia (CLL). We report the identification of
p.(I78T), previously ranked with conflicting interpretations of pathogenicity, as a founder pathogenic variant among Ashkenazi Jews (AJs) and describe its unique clinical landscape. A directed database search was conducted for individuals referred for genetic counselling from 2018 to 2023. Demographic, clinical, genetic, and pathological data were collected and analyzed. Eleven carriers, 25 to 67 years old, from ten apparently unrelated families were identified. Carriers had a total of 30 primary malignancies (range 1-6); nine carriers (82%) had recurrent melanoma between the ages of 25 and 63 years, three carriers (27%) had desmoid tumors, three (27%) had papillary thyroid cancer (PTC), and five women (63% of female carriers) had breast cancer between the ages of 44 and 67 years. Additional tumors included CLL; sarcomas; endocrine tumors; prostate, urinary, and colorectal cancers; and colonic polyps. A review of a local exome database yielded an allelic frequency of the variant of 0.06% among all ethnicities and of 0.25% in AJs. A shared haplotype was found in all carriers tested.
p.(I78T) is a founder disease-causing variant associated with early-onset melanoma and additional various solid malignancies with a high tumor burden. We advocate testing for this variant in high-risk patients of AJ descent. The inclusion of
in germline panels for various types of cancer is warranted.
Background Although colonoscopy is the criterion standard for detecting colorectal adenomas and cancers, a significant percentage of adenomas are missed. Objective To compare forward-viewing with ...ultrawide-viewing colonoscopy in the detection of simulated colon polyps in an in vitro colon model. Design Prospective, multicenter. Setting Six endoscopy units (3 in the United States and 3 in Israel). Patients In vitro colon model with simulated colon polyps (n = 21 metallic beads). Interventions Detection of simulated colon polyps on colonoscope withdrawal. Main Outcome Measurements Incremental detection of simulated colon polyps and endoscopist evaluation of the usability, visibility, and maneuverability of ultrawide-viewing colonoscopy. Results On forward-viewing colonoscopy, the number of simulated polyps (mean ± standard deviation) detected per endoscopist was 11.1 ± 2.3 polyps, a 52.9% detection rate. Simulated polyp detection rates per colon segment were 3.0 ± 0.93 (60.0%) right colon, 2.4 ± 0.87 (48.0%) transverse colon, and 5.7 ± 1.5 (51.8%) left colon. On ultrawide-viewing colonoscopy, the simulated polyp detection rate per endoscopist significantly increased to 18.0 ± 1.98 polyps, an overall 85.7% polyp detection rate ( P < .001). Simulated polyp detection rates were also significantly higher by using the ultrawide-viewing mode in each colon segment, 4.5 ± 0.65 polyps (90.0%) right colon, 4.0 ± 0.87 (80.0%) polyps transverse colon, and 9.6 ± 1.28 polyps (87.3%) left colon (all comparisons, P < .001). Importantly, the ultrawide-viewing mode detected significantly more “hidden” simulated polyps (81.9% vs 31.9%, P < .0001). Limitations Nonrandomized design, use of a colon model, and “simulated” colon polyps. Conclusions Ultrawide-view colonoscopy significantly improved simulated polyp detection in a colon model. Clinical studies in human subjects should be pursued to further evaluate this new endoscopic technology.
Background The Sightline ColonoSight (CS) colonoscopy system presents 3 technologic advances: (1) disposable components protect the reusable parts from contact with colonic contents, eliminating the ...need for disinfection between procedures, (2) an air-pressure–powered engine assists in colonoscope advancement, (3) light emitting diode (LED) illumination eliminates the need for fiber optics and an external light source. Objectives To study the operation, performance, and safety of the Sightline CS colonoscopy system. Design The system was tested during colonoscopy in animals and in human pilot studies. An in vitro dye diffusion test, and bacterial cultures (obtained after using the colonoscope in animals and humans) were performed to ascertain the protective integrity of the disposable components. Setting Animal centers, hospitals in Israel and Italy, and office endoscopy centers in the United States. Patients Thirty-three volunteers and 145 patients who required a colonoscopy for various indications. Interventions Colonoscopy, polypectomy, biopsy, and coagulation. Main Outcome Measures Complications, system function, cecal intubation, and colonoscopy time. Results The Sightline CS system performed well during a colonoscopy in 19 animals and 178 patients, without complications. Dye studies and bacterial cultures showed no transfer of dye molecules or bacterial organisms across the protective, disposable components. Limitations This is an observational pilot study, with no comparative group. Conclusions The new Sightline CS colonoscopy system performed well. The disposable components eliminated the need for disinfection of the colonoscope between procedures. Advancement of the colonoscope in the colon was helped by self propulsion of the instrument affected by an air-pressure–powered engine. LED illumination eliminated the need for fiber optics and an external light source.
Background Performing a full-thickness intestinal wall resection of a sessile polyp located on the mesenteric side with a compression clip may lead to compression of mesenteric vessels. The ...application of such a clip may therefore cause a compromised blood supply in the particular bowel segment, leading to perforation. Objective To evaluate the performance of a newly developed, nitinol compression clip, called the NiTi clamp, for full-thickness resection of the bowel wall, while the clip is deliberately deployed endoluminally on the mesenteric side. Design Prospective animal study. Multinational, multidisciplinary; gastroenterology and general surgery, research cooperation. Setting Animal research laboratory. Intervention Six pigs were operated upon and endoscopically evaluated and then killed after 3 weeks. Linear compression closure clips based on nitinol springs were used. Three longitudinal enterotomies were performed: in the cecum, spiral colon, and proximal rectum. Four clips were deployed in each animal. Main Outcome Measurements A total of 23 clips were deployed. The average expulsion day was 9 days. Results All but 3 clips were normally expelled. One pig developed bowel ischemia due to intussusception. In endoscopic procedures, no signs of significant segmental mucosal ischemia were found. The macroscopic appearance of the compression closure lines was thin and delicate, but epithelialization was significantly delayed at 5 sites. Limitation Differences between porcine and human colorectal anatomy. Conclusion Full-thickness clamping of the bowel with the NiTi clamp, including the local mesenteric vasculature, does not significantly impair local healing of the clamp site and gives hope to further development of novel full-thickness endoscopic resection technologies.
Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated ...lymphocytes circulating to the gastrointestinal tract.
We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis. Patients were randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks. The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12, with higher scores indicating more severe disease; subscores range from 0 to 3, with higher scores indicating more severe disease. The primary outcome was clinical remission (Mayo Clinic score ≤2, with no subscore >1) at 8 weeks.
The primary outcome occurred in 16% of the patients who received 1 mg of ozanimod and in 14% of those who received 0.5 mg of ozanimod, as compared with 6% of those who received placebo (P=0.048 and P=0.14, respectively, for the comparison of the two doses of ozanimod with placebo). Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant; therefore, the hierarchical testing plan deemed the analyses of secondary outcomes exploratory. Clinical response (decrease in Mayo Clinic score of ≥3 points and ≥30% and decrease in rectal-bleeding subscore of ≥1 point or a subscore ≤1) at 8 weeks occurred in 57% of those receiving 1 mg of ozanimod and 54% of those receiving 0.5 mg, as compared with 37% of those receiving placebo. At week 32, the rate of clinical remission was 21% in the group that received 1 mg of ozanimod, 26% in the group that received 0.5 mg of ozanimod, and 6% in the group that received placebo; the rate of clinical response was 51%, 35%, and 20%, respectively. At week 8, absolute lymphocyte counts declined 49% from baseline in the group that received 1 mg of ozanimod and 32% from baseline in the group that received 0.5 mg. The most common adverse events overall were anemia and headache.
In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety. (Funded by Receptos; TOUCHSTONE ClinicalTrials.gov number, NCT01647516.).
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