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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 -
Radiology and Oncology Jun 2024Patients with familial adenomatous polyposis (FAP) develop early colorectal adenomas and if left untreated, progression to cancer is an inevitable event. Prophylactic... (Review)
Review
BACKGROUND
Patients with familial adenomatous polyposis (FAP) develop early colorectal adenomas and if left untreated, progression to cancer is an inevitable event. Prophylactic surgery does not prevent further development of cancer in the rectal remnant, rectal cuff in patients with ileal pouch anal anastomosis (IPAA) and even on the ileal mucosa of the pouch body. The aim of this review is to assess long-term rates of cancer and adenoma development in patients with FAP after prophylactic surgery and to summarise current recommendations for endoscopic management and surveillance of these patients.
MATERIALS AND METHODS
A systematic literature search of studies from January 1946 through to June 2023 was conducted using the PRISMA checklist. The electronic database PubMed was searched.
RESULTS
Fifty-four papers involving 5010 patients were reviewed. Cancer rate in the rectal remnant was 8.8-16.7% in the western population and 37% in the eastern population. The cumulative risk of cancer 30 years after surgery was 24%. Mortality due to cancer in the rectal remnant is 1.1-11.1% with a 5-year survival rate of 55%. The adenoma rate after primary IPAA was 9.4-85% with a cumulative risk of 85% 20 years after surgery and a cumulative risk of 12% for advanced adenomas 10 years after surgery. Cumulative risk for adenomas after ileorectal anastomosis (IRA) was 85% after 5 and 100% after 10 years. Adenomas developed more frequently after stapled (33.9-57%) compared to hand-sewn (0-33%) anastomosis. We identified reports of 45 cancers in patients after IPAA of which 30 were in the pouch body and 15 in the rectal cuff or at the anastomosis.
CONCLUSIONS
There was a significant incidence of cancer and adenomas in the rectal remnant and ileal pouch of FAP patients during the long-term follow-up. Regular endoscopic surveillance is recommended, not only in IRA patients, but also in pouch patients after proctocolectomy.
Topics: Humans; Adenomatous Polyposis Coli; Proctocolectomy, Restorative; Colectomy; Adenoma; Prophylactic Surgical Procedures; Colorectal Neoplasms
PubMed: 38860690
DOI: 10.2478/raon-2024-0029 -
BioRxiv : the Preprint Server For... May 2024Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood....
BACKGROUND
Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics.
METHODS
A Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused on ( ), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice ( ) and patients (FAP, Lynch Syndrome, PJS, and JPS).
RESULTS
The MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced upon infection, but not in response to infection with other enteric bacteria or probiotics. MACS induction upon infection was higher in organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs.
CONCLUSIONS
Computational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.
PubMed: 38853996
DOI: 10.1101/2024.05.26.595902 -
Frontiers in Oncology 2024PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to...
BACKGROUND
PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions.
OBJECTIVE
To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images.
METHODS
PolyDeep Image Classification (PIC) is an diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test.
RESULTS
The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001).
CONCLUSION
PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps.
PubMed: 38846970
DOI: 10.3389/fonc.2024.1393815 -
Pathology Oncology Research : POR 2024Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental...
Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.
Topics: Humans; Gardner Syndrome; Female; Adolescent; Genetic Testing; Tooth Abnormalities; Early Diagnosis; Pedigree
PubMed: 38807857
DOI: 10.3389/pore.2024.1611768 -
Caspian Journal of Internal Medicine 2024Colorectal cancer could be developed from adenomatous polyp. The study aimed to evaluate the diagnostic significance of stromal and epithelial CD10 (Neprilysin)...
BACKGROUND
Colorectal cancer could be developed from adenomatous polyp. The study aimed to evaluate the diagnostic significance of stromal and epithelial CD10 (Neprilysin) expression in patients with colorectal adenocarcinoma and adenomatous polyps.
METHODS
This cross-sectional study was conducted on 141 patients with colorectal adenocarcinoma and adenomatous polyps referred to Ayatollah Rouhani Hospital from March 2020 to March 2021. Differential diagnoses of colorectal adenocarcinoma and adenomatous polyps were made colonoscopically, and then samples were taken from the lesions. The pathologists confirmed the final diagnosis as colorectal adenocarcinoma, high-grade or low-grade adenomatous polyps. The stromal and epithelial CD10 expression was evaluated by immunohistochemistry. The data was analyzed by SPSS 22 software (p<0.05).
RESULTS
Sixty-five (46.1%) of the cases were low-grade polyps that were included positive (4 cases; 6.20%) and negative (61 cases; 93.80%) CD10 expression (P=0.001), also 76 (53.9%) of them were either high-grade polyps (21 cases) or adenocarcinomas (21 cases). Also, epithelial CD10 expression was significantly higher in the well-differentiated adenocarcinoma (38 cases) group than moderate (13 cases) and poor (4 cases) groups (P =0.001). Moreover, the CD10 expression level in the adenomatous polyps (10 positive cases and 76 negative cases) was correlated with the degree of dysplasia (P = 0.001) and the presence of tumor invasion (8 positive cases and 133 negative cases) (P = 0.001).
CONCLUSION
The CD10 expression is associated with an increased degree of dysplasia and the presence of tumor invasion in patients with pre-neoplastic lesions and colorectal adenocarcinoma.
PubMed: 38807719
DOI: 10.22088/cjim.15.2.228 -
MedRxiv : the Preprint Server For... May 2024-associated polyposis (MAP) is an autosomal recessive disorder where the inheritance of constitutional biallelic pathogenic variants predisposes a person to the...
-associated polyposis (MAP) is an autosomal recessive disorder where the inheritance of constitutional biallelic pathogenic variants predisposes a person to the development of adenomas and colorectal cancer (CRC). It is also associated with extracolonic and extraintestinal manifestations that may overlap with the phenotype of familial adenomatous polyposis (FAP). Currently, there are discrepancies in the literature regarding whether certain phenotypes are truly associated with MAP. This narrative review aims to explore the phenotypic spectrum of MAP to better characterise the MAP phenotype. A literature search was conducted to identify articles reporting on MAP-specific phenotypes. Clinical data from 2109 MAP patients identified from the literature showed that 1123 patients (53.2%) had CRC. Some patients with CRC had no associated adenomas, suggesting that adenomas are not an obligatory component of MAP. Carriers of the two missense founder variants, and possibly truncating variants, had an increased cancer risk when compared to those who carry other pathogenic variants. It has been suggested that somatic G:C>T:A transversions are a mutational signature of MAP, and could be used as a biomarker in screening and identifying patients with atypical MAP, or in associating certain phenotypes with MAP. The extracolonic and extraintestinal manifestations that have been associated with MAP include duodenal adenomas, duodenal cancer, fundic gland polyps, gastric cancer, ovarian cancer, bladder cancer and skin cancer. The association of breast cancer and endometrial cancer with MAP remains disputed. Desmoids and Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPEs) are rarely reported in MAP, but have long been seen in FAP patients, and thus could act as a distinguishing feature between the two. This collection of MAP phenotypes will assist in the assessment of pathogenic variants using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) Variant Interpretation Guidelines, and ultimately improve patient care.
PubMed: 38798681
DOI: 10.1101/2024.05.15.24307143 -
Pharmaceutics May 2024Familial adenomatous polyposis (FAP) is a rare disease characterized by the development of adenomatous polyps in the colon and rectum already in adolescence. If left... (Review)
Review
Familial adenomatous polyposis (FAP) is a rare disease characterized by the development of adenomatous polyps in the colon and rectum already in adolescence. If left untreated, patients develop colorectal cancer (CRC) with a 100% probability. To date, the gold standard of FAP management is surgery, which is associated with morbidity and mortality. A chemopreventive agent capable of delaying, preventing and reversing the development of CRC has been sought. Several classes of drugs have been used but to date no chemopreventive drug has been found for the management of this disease. In recent years, the importance of estrogen receptors in FAP and CRC, particularly the β subtype, has emerged. Indeed, the expression of the latter is strongly reduced in adenomatous polyps and CRC and is inversely correlated with the aggressiveness of the disease. Since phytoestrogens have a high affinity for this receptor, they have been suggested for use as chemopreventive agents in FAP and CRC. A combination of phytoestrogens and insoluble fibres has proved particularly effective. In this review, the various mechanisms of action of phytoestrogens were analyzed and the effectiveness of using phytoestrogens as an effective chemopreventive strategy was discussed.
PubMed: 38794302
DOI: 10.3390/pharmaceutics16050640 -
International Journal of Environmental... Apr 2024The Alaska Native Tribal Health Consortium (ANTHC) participated in the United States Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP)...
The Alaska Native Tribal Health Consortium (ANTHC) participated in the United States Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP) from 2009 to 2015. We conducted a descriptive evaluation of ANTHC CRCCP demographics, quality measures, and clinical outcomes, including screening methods employed within the program and screening outcomes. There were 6981 program screenings completed, with the majority (81.3%) of people screened in the 50-75 year age group. Colonoscopy was the primary screening test used, accounting for 6704 (96.9%) of the screening tests. Quality of colonoscopy was high: adequate bowel preparation was reported in 98.2% of colonoscopies, cecal intubation rate was 98.9%, and the adenoma detection rate was 38.9%. A high proportion (58.9%) of colonoscopies had an initial finding of polyps or lesions suspicious for cancer; 41.2% of all colonoscopies had histological confirmation of either adenomatous polyps (40.6%) or cancer (0.5%). The ANTHC CRCCP successfully increased CRC screening among American Indian and Alaska Native peoples living in Alaska; this was achieved primarily through high-quality colonoscopy metrics. These data support a continued focus by the Alaska Native Tribal Health Consortium and its tribal health partners on increasing CRC screening and reducing cancer mortality among Alaska Native peoples.
Topics: Humans; Colorectal Neoplasms; Middle Aged; Alaska Natives; Male; Female; Aged; Colonoscopy; Early Detection of Cancer; Alaska; United States; Adult
PubMed: 38791767
DOI: 10.3390/ijerph21050552 -
PeerJ 2024Polyunsaturated fatty acids (PUFAs) are vital nutrients in human physiology and are implicated in various chronic diseases. However, the relationship between PUFAs and...
Polyunsaturated fatty acids (PUFAs) are vital nutrients in human physiology and are implicated in various chronic diseases. However, the relationship between PUFAs and gastric polyps remains unclear. This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess PUFA levels in the serum of 350 patients, along with analyzing the ω-6 to ω-3 ratio. The results revealed significant differences in the levels of C16:1, C18:1, C18:2, α-C18:3, γ-C18:3, C20:1, C20:4, C20:5, ω-3-C22:5, ω-6-C22:5, and C22:6, as well as ω-6 to ω-3 ratio between the control and gasteic polyp groups. Moreover, setting the threshold for ω-6: ω-3 at 10 revealed a close correlation between polyp occurrence and this ratio. These findings suggest that PUFAs and the ω-6 to ω-3 ratio hold promise as potential early screening markers for gastric polyps. However, further research is imperative to elucidate the underlying mechanisms and therapeutic potential of PUFAs in managing gastric polyps.
Topics: Humans; Male; Female; Middle Aged; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Tandem Mass Spectrometry; Fatty Acids, Omega-6; Adult; Chromatography, Liquid; Aged; Stomach Neoplasms; Biomarkers; Case-Control Studies; Adenomatous Polyps
PubMed: 38784403
DOI: 10.7717/peerj.17413