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Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review.Familial Cancer Oct 2022Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or... (Review)
Review
Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.
Topics: Female; Humans; Middle Aged; Adenoma; Adenomatous Polyposis Coli; Breast Neoplasms; Colorectal Neoplasms; Deoxyribonuclease (Pyrimidine Dimer); Genetic Predisposition to Disease; Germ-Line Mutation; Male; Adult; Aged
PubMed: 35292903
DOI: 10.1007/s10689-022-00291-3 -
European Journal of Gastroenterology &... Aug 2021Colonoscopy is an important method to diagnose polyps, especially adenomatous polyps. However, the rate of missed diagnoses is relatively high. In this study, we aimed... (Meta-Analysis)
Meta-Analysis
Colonoscopy is an important method to diagnose polyps, especially adenomatous polyps. However, the rate of missed diagnoses is relatively high. In this study, we aimed to determine whether artificial intelligence (AI) improves the polyp detection rate (PDR) and adenoma detection rate (ADR) with colonoscopy. We performed a systematic search in PubMed, Cochrane Library, Embase, and Web of Science databases; the search included entries in the databases up to and including 29 February 2020. Five articles that involved a total of 4311 patients fulfilled the selection criteria. The results of these studies showed that both PDR and ADR increased with the assistance of AI compared with those in control groups {pooled odds ratio (OR) = 1.91 [95% confidence interval (CI) 1.68-2.16] and 1.75 (95% CI 1.52-2.01), respectively}. Good bowel preparation reduced the impact of AI, but significant differences were still apparent in PDR and ADR [pooled OR = 1.69 (95% CI 1.32-2.16) and 1.36 (95% CI 1.04-1.78), respectively]. The characteristics of polyps and adenomas also influenced the results. The average number of polyps and adenomas detected varied significantly by location, and small polyps and adenomas were more likely to be missed. However, the effect of the morphology of polyps and AI-assisted detection needs further studies. In conclusion, AI increases the detection rates of polyps and adenomas in colonoscopy. Without AI assistance, detection rates can be improved with better bowel preparation and training for small polyp and adenoma detection.
Topics: Adenoma; Adenomatous Polyps; Artificial Intelligence; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans
PubMed: 32804846
DOI: 10.1097/MEG.0000000000001906 -
Journal of Medical Internet Research Aug 2021Most colorectal polyps are diminutive and benign, especially those in the rectosigmoid colon, and the resection of these polyps is not cost-effective. Advancements in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most colorectal polyps are diminutive and benign, especially those in the rectosigmoid colon, and the resection of these polyps is not cost-effective. Advancements in image-enhanced endoscopy have improved the optical prediction of colorectal polyp histology. However, subjective interpretability and inter- and intraobserver variability prohibits widespread implementation. The number of studies on computer-aided diagnosis (CAD) is increasing; however, their small sample sizes limit statistical significance.
OBJECTIVE
This review aims to evaluate the diagnostic test accuracy of CAD models in predicting the histology of diminutive colorectal polyps by using endoscopic images.
METHODS
Core databases were searched for studies that were based on endoscopic imaging, used CAD models for the histologic diagnosis of diminutive colorectal polyps, and presented data on diagnostic performance. A systematic review and diagnostic test accuracy meta-analysis were performed.
RESULTS
Overall, 13 studies were included. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD models for the diagnosis of diminutive colorectal polyps (adenomatous or neoplastic vs nonadenomatous or nonneoplastic) were 0.96 (95% CI 0.93-0.97), 0.93 (95% CI 0.91-0.95), 0.87 (95% CI 0.76-0.93), and 87 (95% CI 38-201), respectively. The meta-regression analysis showed no heterogeneity, and no publication bias was detected. Subgroup analyses showed robust results. The negative predictive value of CAD models for the diagnosis of adenomatous polyps in the rectosigmoid colon was 0.96 (95% CI 0.95-0.97), and this value exceeded the threshold of the diagnosis and leave strategy.
CONCLUSIONS
CAD models show potential for the optical histological diagnosis of diminutive colorectal polyps via the use of endoscopic images.
TRIAL REGISTRATION
PROSPERO CRD42021232189; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=232189.
Topics: Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Computers; Diagnostic Tests, Routine; Humans; Narrow Band Imaging
PubMed: 34432643
DOI: 10.2196/29682 -
Endoscopy International Open Jun 2024There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating... (Review)
Review
There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating properties of existing endoscopic severity indices for FAP. We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2023 to identify randomized controlled trials (RCTs) that utilized endoscopic outcomes or studies that evaluated the operating properties of endoscopic disease severity indices in FAP. A total of 134 studies were included. We evaluated scoring indices and component items of scoring indices, such as polyp count, polyp size, and histology. Partial validation was observed for polyp count and size. The most commonly reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal involvement. A single study reported almost perfect interobserver and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden, has been partially validated. It showed substantial interobserver reliability; however, the intra-observer reliability was not assessed. Novel criteria for high-risk gastric polyps have been developed and assessed for interobserver reliability. However, these criteria showed a poor level of agreement. Other scoring indices assessing the anal transition zone, duodenal, and colorectal polyps have not undergone validation. There are no fully validated endoscopic disease severity indices for FAP. Development and validation of a reliable and responsive endoscopic disease severity instrument will be informative for clinical care and RCTs of pharmacological therapies for FAP.
PubMed: 38904059
DOI: 10.1055/a-2330-8037 -
Gastroenterology Research Aug 2018Colorectal cancer (CRC) is a leading cause of death worldwide. Polyp detection rate (PDR) and adenoma detection rate (ADR) are key focus in endoscopic research for CRC...
BACKGROUND
Colorectal cancer (CRC) is a leading cause of death worldwide. Polyp detection rate (PDR) and adenoma detection rate (ADR) are key focus in endoscopic research for CRC screening and prevention. Use of anti-spasmodic agents during colonoscopy to help identify adenomas and polyps has remained a controversial topic. Hyoscine butyl bromide (HBB) is the most commonly used anti-spasmodic agent in patients undergoing colonoscopy. Some randomized controlled trials (RCTs) have questioned the clinical efficacy and safety of routine use of HBB for polyp and adenoma detection rates.
METHODS
We conducted a systematic search in PubMed and MEDLINE from inception until February 10, 2018, for studies which compared HBB with placebo. We used RevMan version 5.3 for analysis. Procedural end-points were polyps, adenomas, and advanced adenoma detection rates, mean number of polyps detected and cecal intubation time.
RESULTS
We included seven RCTs with 2,588 patients in our analysis. A total of 1,301 patients were randomized to HBB arm and 1,287 to the placebo arm. There was no significant difference in the primary outcome of polyp detection rate, 654 in HBB group vs. 616 in the placebo group, (odds ratio (OR) = 1.11, confidence interval (CI) = 0.93 - 1.34, P = 0.25). There was no difference in secondary outcomes of adenoma detection rate, 430 in HBB group vs. 396 in the placebo group, (OR = 1.06, CI = 0.89 - 1.26, P = 0.51), advanced adenoma detection rate, 92 in HBB vs. 95 in placebo group (OR = 0.95, CI = 0.70 - 1.30, P = 0.76), mean number of polyps detected (point estimate = 0.12, CI = 0.00 - 0.23, P = 0.05), adenomatous polyps (OR = 0.84, CI = 0.39 - 1.81, P = 0.65) and cecal intubation time (point estimate = 0.73, CI = -1.98 - 0.52, P = 0.25) between the two groups.
CONCLUSIONS
The use of HBB in patients undergoing colonoscopy does not appear to improve polyp or adenoma detection rates. It showed a non-significant trend of increased mean number of polyps detected with HBB.
PubMed: 30116429
DOI: 10.14740/gr1057w -
International Journal of Colorectal... Apr 2021The ileo-anal pouch (IAP) has been the gold standard procedure for maintenance of bowel continuity after panproctocolectomy for ulcerative colitis, familial adenomatous... (Review)
Review
PURPOSE
The ileo-anal pouch (IAP) has been the gold standard procedure for maintenance of bowel continuity after panproctocolectomy for ulcerative colitis, familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. However, the IAP has an estimated failure rate of 13% at 10 years post-procedure (Tulchinsky et al., Ann Surg 238(2):229-34, 2003), which can result in pouch excision (P.E.). This systematic review aims to synthesise all the available studies reporting post-operative outcomes of P.E. and its impact on patient quality of life (QoL), when available, which have not previously been summarised.
METHODS
PubMed, Embase, Medline and the Cochrane library databases were searched with terms 'Pouch AND excision' OR 'Pouch AND removal' OR 'Pouch AND remove' OR 'IAP AND excision'. All studies reporting post-operative morbidity, mortality or functional outcomes in patients who had P.E. were included. Studies with < 5 patients, non-English studies and conference abstracts were excluded.
RESULTS
14 studies comprising 1601 patients were included. Overall complications varied from 18 to 63% with the most common being persistent perineal sinus (9-40%) or surgical site infection (wound-2 to 30%; intra-abdominal collection-3 to 24%). The mortality rate was between 0.58 and 1.4%. QoL is generally lower in P.E. patients compared to the normal population across various QoL measures and P.E. patients often had urinary and sexual dysfunction post-operatively.
CONCLUSIONS
There is a substantial incidence of complications after P.E.; however, there is no evidence describing QoL pre- and post-P.E. Further longitudinal research comparing QoL in patients undergoing P.E. and other treatment options such as indefinite diversion is required to definitively assess QoL post-procedure.
Topics: Adenomatous Polyposis Coli; Anal Canal; Colitis, Ulcerative; Colonic Pouches; Humans; Postoperative Complications; Proctocolectomy, Restorative; Quality of Life; Retrospective Studies; Treatment Outcome
PubMed: 33471205
DOI: 10.1007/s00384-021-03838-5 -
Clinical Gastroenterology and... Aug 2020Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer... (Review)
Review
BACKGROUND & AIMS
Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes.
METHODS
We searched PubMed through March 2018 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other CRC susceptibility genes, and epigenetic mosaicism.
RESULTS
Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM).
CONCLUSIONS
We found that somatic mosaicism is underdiagnosed but critical for determining the clinical management of patients with de novo polyposis who possibly carry mosaic APC variants, and present a decision tree for the clinical management of these patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an underlying genetic cause, is complex and not fully understood.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Genetic Predisposition to Disease; Humans; Mosaicism; Neoplastic Syndromes, Hereditary
PubMed: 32147591
DOI: 10.1016/j.cgh.2020.02.049 -
Diseases of the Colon and Rectum Jun 2024Patients with familial adenomatous polyposis often require prophylactic colectomy with IPAA to treat or reduce the risk of colorectal neoplasia. However, after surgery,...
BACKGROUND
Patients with familial adenomatous polyposis often require prophylactic colectomy with IPAA to treat or reduce the risk of colorectal neoplasia. However, after surgery, patients are still at some risk of developing pouch polyps and even cancer in both handsewn and stapled anastomoses. Management relies mainly on endoscopic or surgical interventions, whereas chemopreventive agents have a limited role in the management and prevention of pouch neoplasia. Novel endoscopic techniques are evolving and may gradually overtake surgical intervention in selected cases. Because familial adenomatous polyposis is relatively rare, there is a scarcity of data regarding the natural history of pouch polyps and cancer in this population.
OBJECTIVE
This systematic literature review aims to describe the evolution, characteristics, various treatment modalities and their outcomes, and recommended surveillance strategies of pouch neoplasia.
DATA SOURCES
PubMed and Cochrane databases and the International Ileal Pouch Consortium (for expert opinion).
STUDY SELECTION
Studies published between 1990 and 2023 in English were included. Studies reporting neoplastic outcomes of only patients with IBD-related pouch neoplasia were excluded.
MAIN OUTCOME MEASURES
Incidence of pouch neoplasia and its outcomes (successful resections, surgical complications, and mortality).
RESULTS
Thirty-five studies were included.
LIMITATIONS
Most studies focused on patients with IBD-related pouch neoplasia; there were scarce data regarding polyposis patients only. Most cohorts were small and retrospective. Data on interventions were mainly descriptive, and no randomized controlled trials were available.
CONCLUSIONS
Pouch adenomas are common and well managed by endoscopic resections because advanced endoscopic techniques are becoming more available. Additional data are required for defining updated recommendations for either endoscopic or surgical intervention. Pouch cancer is a very rare event and may arise despite surveillance. Continued endoscopic surveillance is key in cancer prevention and early detection. The outcome of cancer cases is poor, and management in a referral center should be advised with tumor board discussions. See video from symposium .
Topics: Humans; Adenomatous Polyposis Coli; Proctocolectomy, Restorative; Colonic Pouches; Colectomy
PubMed: 37878460
DOI: 10.1097/DCR.0000000000003122 -
Journal of Gastrointestinal Surgery :... Dec 2014Temporary loop ileostomy is a routine procedure to reduce the morbidity of restorative proctocolectomy. However, morbidity of ileostomy closure could reduce the benefit... (Review)
Review
BACKGROUND
Temporary loop ileostomy is a routine procedure to reduce the morbidity of restorative proctocolectomy. However, morbidity of ileostomy closure could reduce the benefit of this concept. The objective of this systematic review was to assess the risks of ileostomy closure after restorative proctocolectomy for ulcerative colitis or familial adenomatous polyposis.
MATERIALS AND METHODS
Publications in English or German language reporting morbidity of ileostomy closure after restorative proctocolectomy were identified by Medline search. Two hundred thirty-two publications were screened, 143 were assessed in full-text, and finally 26 studies (reporting 2146 ileostomy closures) fulfilled the eligibility criteria. Weighted means for overall morbidity and mortality of ileostomy closure, rate of redo operations, anastomotic dehiscence, bowel obstruction, wound infection, and late complications were calculated.
RESULTS
Overall morbidity of ileostomy closure was 16.5 %, there was no mortality. Redo operations for complications were necessary in 3.0 %. Anastomotic dehiscence occurred in 2.0 %. Postoperative bowel obstruction developed in 7.6 %, with 2.9 % of patients requiring laparotomy for this complication. Wound infection rate was 4.0 %. Hernia or bowel obstruction as late complications developed in 1.9 and 9.4 %, respectively.
CONCLUSION
The considerable morbidity of ileostomy reversal reduces the overall benefit of temporary fecal diversion. However, ileostomy creation is still recommended, as it effectively reduces the risk of pouch-related septic complications.
Topics: Adenomatous Polyposis Coli; Colitis, Ulcerative; Global Health; Humans; Ileostomy; Morbidity; Postoperative Complications; Proctocolectomy, Restorative; Plastic Surgery Procedures; Reoperation
PubMed: 25231081
DOI: 10.1007/s11605-014-2660-8 -
The Cochrane Database of Systematic... Jan 2017This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental... (Review)
Review
BACKGROUND
This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive.
OBJECTIVES
To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention.
SEARCH METHODS
We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016.
SELECTION CRITERIA
We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable.
MAIN RESULTS
We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution.
AUTHORS' CONCLUSIONS
There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.
Topics: Adenoma; Adenomatous Polyps; Aged; Colorectal Neoplasms; Dietary Fiber; Humans; Middle Aged; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic
PubMed: 28064440
DOI: 10.1002/14651858.CD003430.pub2