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Techniques in Coloproctology Dec 2023First described by Parks and Nicholls in 1978, the ileal pouch-anal anastomosis (IPAA) has revolutionized the treatment of mucosal ulcerative colitis (MUC) and familial... (Review)
Review
BACKGROUND
First described by Parks and Nicholls in 1978, the ileal pouch-anal anastomosis (IPAA) has revolutionized the treatment of mucosal ulcerative colitis (MUC) and familial adenomatous polyposis (FAP). IPAA is fraught with complications, one of which is pouch-vaginal fistulas (PVF), a rare but challenging complication noted in 3.9-15% of female patients. Surgical treatment success approximates 50%. Gracilis muscle interposition (GMI) is a promising technique that has shown good results with other types of perineal fistulas. We present the results from our institution and a comprehensive literature review.
METHODS
A retrospective observational study including all patients with a PVF treated with GMI at our institution from December 2018-January 2000. Primary outcome was complete healing after ileostomy closure.
RESULTS
Nine patients were included. Eight of nine IPAAs (88.9%) were performed for MUC, and one for FAP. A subsequent diagnosis of Crohn's disease was made in five patients. Initial success occurred in two patients (22.2%), one patient was lost to follow-up and seven patients, after further procedures, ultimately achieved healing (77.8%). Four of five patients with Crohn's achieved complete healing (80%).
CONCLUSION
Surgical healing rates quoted in the literature for PVFs are approximately 50%. The initial healing rate was 22.2% and increased to 77.8% after subsequent surgeries, while it was 80% in patients with Crohn's disease. Given this, gracilis muscle interposition may have a role in the treatment of pouch-vaginal fistulas.
Topics: Humans; Female; Cohort Studies; Crohn Disease; Colonic Pouches; Gracilis Muscle; Neoplasm Recurrence, Local; Proctocolectomy, Restorative; Colitis, Ulcerative; Vaginal Fistula; Treatment Outcome; Retrospective Studies; Adenomatous Polyposis Coli; Observational Studies as Topic
PubMed: 38079014
DOI: 10.1007/s10151-023-02880-5 -
United European Gastroenterology Journal Oct 2023The risk of cancer in patients with solitary colorectal juvenile polyps (JPs) is poorly investigated and several studies have reported polyps with dysplastic and...
INTRODUCTION
The risk of cancer in patients with solitary colorectal juvenile polyps (JPs) is poorly investigated and several studies have reported polyps with dysplastic and adenomatous alterations. We aimed to investigate the long-term risk of cancer and mortality in these patients by merging data from national registers and comparing them to a matched control cohort.
MATERIALS AND METHODS
Patients with a solitary JP were identified in The Danish National Pathology Register and Data Bank (DNPR). The included patients were matched on sex, age, and place of birth with 50 controls. The groups were then analyzed for risk of cancer using the Danish Cancer Registry and mortality using the Danish Cause of Death Registry.
RESULTS
We identified 1781 patients with solitary JPs and matched them with 83,713 controls. The mean follow-up time was 7.65 years for cases and 7.36 years for controls. The risk of cancer, including colorectal cancer, did not differ for the two groups and when adjusting for sex and year of birth, the hazard ratio (HR) was 1.15 (confidence interval [CI] 95% 0.94-1.41, p = 0.162). There was no increased risk of death (HR: 1.07, CI 95% 0.88-1.30, p = 0.486). The risk did not differ for different age groups or sex.
CONCLUSION
There is no increased risk of cancer or mortality for patients with solitary colorectal JPs. Thus, endoscopic follow-up may be safely omitted in these patients.
Topics: Humans; Cohort Studies; Intestinal Polyps; Intestinal Polyposis; Adenoma; Colorectal Neoplasms
PubMed: 37498302
DOI: 10.1002/ueg2.12441 -
The American Journal of Gastroenterology Apr 2024
Topics: Humans; Ileostomy; Colorectal Neoplasms; Adenomatous Polyposis Coli
PubMed: 38235707
DOI: 10.14309/ajg.0000000000002657 -
The American Journal of Gastroenterology Oct 2023
Topics: Humans; Colorectal Neoplasms; Adenomatous Polyposis Coli; Intestinal Polyposis
PubMed: 37335175
DOI: 10.14309/ajg.0000000000002372 -
BMC Gastroenterology Jan 2024Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional...
BACKGROUND
Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional white light imaging (WLI) and image-enhanced endoscopic (IEE) techniques such as narrow-band imaging (NBI), linked color imaging (LCI) and blue laser imaging (BLI) plays pivotal role in H. pylori diagnosis. This study aimed to determine diagnostic performance of real-time endoscopy between WLI and other IEE techniques for diagnosis of H. pylori infection.
METHODS
This prospective study compared endoscopic images by gastroscopy using WLI and IEE techniques (LCI, Magnifying-BLI, and Magnifying-NBI) at Thammasat University Hospital, Thailand between January 2020, and July 2021. All participants underwent gastroscopy. Three biopsies at gastric antrum and two biopsies at body were obtained for H.pylori diagnosis. H. pylori infection was defined as a positive test of either one of the following tests: rapid urease test, histopathology, H. pylori culture.
RESULTS
Of 167 dyspeptic patients undergoing gastroscopy, 100 were enrolled in this study. Overall H. pylori infection was 40%. Patients had the mean age of 59.1 years and 53% were males. Enlarged gastric folds and antral nodularity can predict H. pylori infection with 100% PPV, while fundic gland polyps and red streak provided 100% PPV for exclusion of H. pylori infection on WLI. Sensitivity, specificity, PPV, NPV and accuracy for diagnosis of H. pylori infection for WLI were 80%, 71.7%, 65.3%, 84.3% and 75% respectively, while those for LCI were 90%, 70%, 66.7%, 91.3% and 78% respectively. M-NBI and M-BLI endoscopy demonstrated elongated pits in H. pylori-positive patients. Sensitivity, specificity, PPV, NPV and accuracy for M-BLI were 95%, 80%, 76%, 96% and 86% respectively, whereas those for M-NBI were 92.5%, 86.7%, 82.2%, 94.6% and 89% respectively. Sensitivity of M-BLI was better than WLI, while sensitivities of LCI and M-NBI were also numerically higher than WLI without statistical difference (M-BLI 95%vs.WLI 80%, p = 0.03; M-NBI 92.5%vs.WLI 80%, p = 0.13; LCI 90%vs.WLI 80%, p = 0.22). Sensitivities of all IEE modes were not different from one another (LCI 90%vs.M-BLI 95%, p = 0.50; LCI 90%vs.M-NBI 92.5%, p = 1.00, M-BLI 95%vs.M-NBI 92.5%, p = 1.00).
CONCLUSIONS
M-BLI significantly improved sensitivity of real-time endoscopic diagnosis of H. pylori infection compared with WLI. Enlarged gastric folds and antral nodularity could be reliable predictors for H. pylori infection, while fundic gland polyps and red streak could be important endoscopic findings for H. pylori-negative mucosa.
Topics: Male; Humans; Middle Aged; Female; Stomach Neoplasms; Helicobacter pylori; Helicobacter Infections; Prospective Studies; Endoscopy, Gastrointestinal; Polyps; Adenomatous Polyps
PubMed: 38273222
DOI: 10.1186/s12876-024-03132-y -
Cancer Letters Mar 2024WNT/β-catenin signaling is aberrantly activated in colorectal cancer (CRC) mainly by loss-of-function mutations in adenomatous polyposis coli (APC) and is involved in...
WNT/β-catenin signaling is aberrantly activated in colorectal cancer (CRC) mainly by loss-of-function mutations in adenomatous polyposis coli (APC) and is involved in tumor progression. Tankyrase inhibitors, which suppress WNT/β-catenin signaling, are currently in pre-clinical and clinical trials. However, the mechanisms of resistance to tankyrase inhibitors remain unclear. In this study, we established tankyrase inhibitor-resistant CRC cells, JC73-RK100, from APC-mutated patient-derived CRC cells. JC73-RK100 cells and several CRC cell lines were sensitive to tankyrase inhibitors at low concentrations but were resistant at high concentrations, showing an intrinsic/acquired bell-shaped dose response. Mechanistically, tankyrase inhibitors at high concentrations promoted BRD3/4-dependent E2F target gene transcription and over-activated cell cycle progression in these cells. BET inhibitors canceled the bell-shaped dose response to tankyrase inhibitors. Combination of tankyrase and BET inhibitors significantly suppressed tumor growth in a mouse xenograft model. These observations suggest that the combination of tankyrase and BET inhibitors may be a useful therapeutic approach to overcome the resistance of a subset of CRCs to tankyrase inhibitors.
Topics: Animals; Humans; Mice; Adenomatous Polyposis Coli; Antineoplastic Agents; beta Catenin; Cell Line, Tumor; Colorectal Neoplasms; Disease Models, Animal; Tankyrases; Wnt Signaling Pathway
PubMed: 38216082
DOI: 10.1016/j.canlet.2024.216632 -
Journal of Gastroenterology and... Nov 2023The current procedure for identifying hereditary colorectal cancer (HCRC) is time consuming in clinical practice. This study aimed to develop a time-saving approach to...
BACKGROUND AND AIM
The current procedure for identifying hereditary colorectal cancer (HCRC) is time consuming in clinical practice. This study aimed to develop a time-saving approach to diagnosing HCRC.
METHODS
A total of 100 suspected HCRC patients were prospectively enrolled (cohort 1) and 116 colorectal cancer patients with DNA mismatch repair-deficient were retrospectively included (cohort 2). Next-generation sequencing (NGS) tests were performed on tumors and matched white blood cells (WBCs) or normal tissues. Using the conventional method upon WBC/normal tissue-based NGS data as a reference, the performance of the ColonCore method using tumor-only-based NGS data in predicting germline variants was explored in cohort 1 and validated in cohort 2.
RESULTS
In cohort 1, the ColonCore method diagnosed 17 Lynch syndrome (LS) and 14 familial adenomatous polyposis (FAP); and by the conventional method, the cases were 16 and 10, respectively. The ColonCore method showed sensitivities of 100% in diagnosing LS (positive predictive value [PPV] 94.1%) and FAP (PPV 71.4%). Moreover, two of seven patients with multiple adenomas/polyps who did not meet existing clinical criteria for HCRC were predicted to harbor germline variants in APC and MUTYH. Additionally, the sensitivity of the ColonCore method in identifying LS patients from cohort 2 reached 85.7% with a PPV of 85.7%.
CONCLUSION
The ColonCore method might be an acceptable tool for predicting germline variants associated with HCRC. Our work indicates the essentiality of NGS tests in CRC patients for precision diagnosis and treatment.
Topics: Humans; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; East Asian People; Germ-Line Mutation; Retrospective Studies
PubMed: 37749864
DOI: 10.1111/jgh.16319 -
Genes Dec 2023Adult pancreatoblastoma (PBL) is a rare pancreatic malignancy, with recent evidence suggesting a possible link to familial adenomatous polyposis (FAP). This study aims... (Review)
Review
BACKGROUND
Adult pancreatoblastoma (PBL) is a rare pancreatic malignancy, with recent evidence suggesting a possible link to familial adenomatous polyposis (FAP). This study aims to review the latest evidence and explore a possible association between adult PBL and FAP.
METHODS
Two independent literature reviews were conducted: (1) on PBL and FAP, and (2) on PBL in the adult population not diagnosed with FAP.
RESULTS
Out of 26 articles on PBL and FAP screened, 5 were selected for systematic review, including 1 additional case. We identified eight FAP-related PBL cases, with a median age of 40 (IQR: 34-50). Of these, seven (87%) occurred in adults. We found 65 cases of adult PBL not FAP-related; thus, 7 out of 65 cases (10.7%) of adult PBL reported in the literature are associated with a clinical diagnosis of FAP or were carriers of germline pathogenic variants (GPVs).
CONCLUSION
Data suggest a non-random association between adult PBL and FAP. Further research is essential to optimise surveillance protocols and develop more effective treatment strategies.
Topics: Adult; Humans; Adenomatous Polyposis Coli; Germ-Line Mutation; Pancreatic Neoplasms
PubMed: 38254934
DOI: 10.3390/genes15010044 -
Frontiers in Oncology 2024Colorectal cancer (CRC) is considered the most prevalent synchronous malignancy in patients with gastric cancer. This large retrospective study aims to clarify...
BACKGROUND
Colorectal cancer (CRC) is considered the most prevalent synchronous malignancy in patients with gastric cancer. This large retrospective study aims to clarify correlations between gastric histopathology stages and risks of specific colorectal neoplasms, to optimize screening and reduce preventable CRC.
METHODS
Clinical data of 36,708 patients undergoing gastroscopy and colonoscopy from 2005-2022 were retrospectively analyzed. Correlations between gastric and colorectal histopathology were assessed by multivariate analysis. Outcomes of interest included non-adenomatous polyps (NAP), conventional adenomas (CAs), serrated polyps (SPs), and CRC. Statistical analysis used R version 4.0.4.
RESULTS
Older age (≥50 years) and infection (HPI) were associated with increased risks of conventional adenomas (CAs), serrated polyps (SPs), non-adenomatous polyps (NAP), and colorectal cancer (CRC). Moderate to severe intestinal metaplasia specifically increased risks of NAP and CAs by 1.17-fold (95% CI 1.05-1.3) and 1.19-fold (95% CI 1.09-1.31), respectively. For CRC risk, low-grade intraepithelial neoplasia increased risk by 1.41-fold (95% CI 1.08-1.84), while high-grade intraepithelial neoplasia (OR 3.76, 95% CI 2.25-6.29) and gastric cancer (OR 4.81, 95% CI 3.25-7.09) showed strong associations. More advanced gastric pathology was correlated with progressively higher risks of CRC.
CONCLUSION
Precancerous gastric conditions are associated with increased colorectal neoplasm risk. Our findings can inform screening guidelines to target high-risk subgroups, advancing colorectal cancer prevention and reducing disease burden.
PubMed: 38444677
DOI: 10.3389/fonc.2024.1320020 -
Molecular Cancer Research : MCR Jun 2024The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This...
UNLABELLED
The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA.
IMPLICATIONS
PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.
Topics: Humans; Glycosylphosphatidylinositols; Duodenal Neoplasms; Mutation; Adenomatous Polyposis Coli; Membrane Proteins; Carcinogenesis; Male; Female
PubMed: 38546397
DOI: 10.1158/1541-7786.MCR-23-0810