Adenomatous Polyposis Research Articles

The relationships between Risk Factors and the changes of Histopathological of Tissue Colon Cancer in Iraq Patients

The transformation of an ordinary cell into a cancerous one could be a dynamic process which often involves the approval of oncogenes as well as deactivation of tumor suppressor properties (alterations). Most changes are emptied by cellular genome dauntlessness and repair components. In any case, many genetic changes give cells an advancement advantage and unused capacities, driving to their neoplastic alter. As other cancers, like melanoma, sarcoma, and lymphoma, could affect the colon, colon cancer, also known as colon carcinoma, affects the epithelium of colon. The uncontrolled proliferation regarding colorectal epithelial cells might be a hallmark of colorectal cancer (CRC). The multistep carcinogenesis hypothesis states that pigment cells go through a sequence of atomic alterations before they become totally dangerous cells. The inactivation related to the Adenomatous polyposis coli (APC) signaling pathway is the most frequent hereditary cause of activation. The pathology of damage includes oncogene changes, tumor suppressor qualities, and probably many signaling pathways, which put cancers at risk of metastasis. In advanced nations, CRC has a high disease-specific mortality rate and impacts over a million individuals annually. Worldwide, CRC ranks 3 rd in terms of the incidence in both women and men. Africa and Central and South Asia have experienced the biggest drops in CRC, whereas New Zealand, Australia, North America, and Europe have experienced highest change rates.

Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants.

Monoallelic germline MBD4 pathogenic variants were recently reported to cause a predisposition to uveal melanoma, associated with a specific tumor mutational signature and good response to immunotherapy. Monoallelic tumor pathogenic variants have also been described in brain tumors, breast cancers, and myxofibrosarcomas, whereas biallelic germline MBD4 pathogenic variants have been involved in a recessive hereditary adenomatous polyposis and a specific type of acute myeloid leukemia. We analyzed MBD4 for all patients with a diagnosis of uveal melanoma at Institut Curie since July 2021 and in the 3240 consecutive female probands explored at the Institut Curie for suspicion of predisposition to breast cancer between July 2021 and February 2023. We describe 25 families whose probands carry a monoallelic germline pathogenic variant in MBD4. Eighteen of these families presented with uveal melanoma (including a case patient with multiple uveal melanoma), and 7 families presented with breast cancer. Family histories showed the first familial case of uveal melanoma in monoallelic MBD4 pathogenic variant carriers and other various types of cancers in relatives, especially breast, renal, and colorectal tumors. Monoallelic MBD4 pathogenic variant may explain some cases of familial and multiple uveal melanoma as well as various cancer types, expanding the tumor spectrum of this predisposition. Further genetic testing in relatives combined with molecular tumor analyses will help define the tumor spectrum and estimate each tumor's risk.

Gardner's Syndrome—A Case Report and Brief Literature

AbstractGardner's syndrome has been recognized as a hereditary affliction that is autosomal in nature. This disorder is known to exhibit characteristics of familial adenomatous polyposis, of which it is also considered a variation. The features of this syndrome include the gradual development of osteomas and epidermoid cysts, including a characteristic feature that is the noted presence of intestinal polyps, which are generally multiple in number. Additionally, dental anomalies have been observed and recorded in a sizeable ratio of cases encompassing an increased frequency of multiple odontomas that are benign tumors linked to the development of a tooth and tooth agenesis/hypodontia that refers to developmental absence of one or more teeth. The other dental ascertainment includes abnormal morphology of the tooth/teeth as well as the presence of supernumerary teeth and impacted or unerupted teeth. This case report outlines the case of a 59-year-old male patient who had reported to the clinic, and was then diagnosed with Gardner's syndrome post a thorough examination. On radiographic examination, the manifestation of multiple osteomas in the frontal bone was revealed. The presence of a motley of diffused benign lesions of the bone in both the upper and lower jaw as well as the presence of an epidermoid cyst on the scalp was suggestive of an exemplar presentation of Gardner's syndrome.

A novel APC mutation associated with Gardner syndrome in a Chinese family

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

Psychiatric and Educational Aspects of Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Nonexposed Individuals.

Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses ( International Classification of Disease, 10th Revision ), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP ( P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25-2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17-1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19-2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20-1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09-2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10-3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24-2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26-2.70, P = 0.002). Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased likelihood of needing antidepressants and antipsychotics.

Microcystic Stromal Tumor of ovary; Report of a rare entity

Abstract Introduction/Objective Microcystic stromal tumor (MCST) of the ovary is an extremely rare subtype of sex cord- stromal neoplasm first described by Irving and Young in 2009. MSCT is characterized by morphology with microcyst structure, solid cellular areas, and hyalinized fibrous stroma. The most reported tumors were stage I with good prognosis. Methods/Case Report We report a rare case of a microcystic stromal tumor of right ovary in a postmenopausal woman, measuring 25 cm in greatest dimension. The present patient underwent right ovarian tumor resection. Gross examination showed that the tumor was solid and cystic. Immunohistochemically, the tumor expressed CD10, WT1, cyclin D1 and vimentin, and nuclear immunoreactivity for β-catenin but negative for α-inhibin, calretinin, CK AE1/AE3, PLAP, SALL-4, CK7, P53, EMA, CD99, AFP, desmin, CgA, E-cadherin, and melanA. Next Generation Sequencing (NGS) showed rare, pathogenic, gain of function mutation CTNNB1 pT41I. The patient is free of disease at 1-year follow up. Results (if a Case Study enter NA) NA Conclusion MCST is a rare stromal tumor of the ovary. These tumors are considered benign neoplasms because almost all cases display unilateral, localized lesions and have benign outcomes, except for one recurrent case with familial adenomatous polyposis and another initial metastatic case with a CTNNB1 mutation (Zhang Y et al. Hum Pathol 2018, 78:171). MCST is histologically characterized by a microcystic growth pattern, solid cellular areas, and intervening hyalinized stroma, accompanied by immunohistochemical evidence of sex cord-stromal differentiation. Accumulation of nuclear -catenin was reported to be relevant to the pathogenesis of MCST (Maeda D et al. Am J Surg Pathol 2011, 35:1429). More specifically, Maeda et al. observed two cases of ovarian MCST that exhibited a CTNNB1 point mutation in exon 3 and strong nuclear immunoreactivity for -catenin. Other cases exhibited alterations of APC, which is associated with familial adenomatous polyposis (Lee SH et al. Genes Chromosomes Cancer 2015, 54: 353). MCST pathogenesis is linked to -catenin stabilization involving -catenin/Wnt signaling. In our case we found a rare pathogenic, gain of function CTNNB1 T41I c.122C&amp;gt;T mutation which maps within a Gsk3b phosphorylation site of the Ctnnb1 protein (UniProt.org). T41I is predicted to confer a gain of function to Ctnnb1 as demonstrated by nuclear accumulation of Ctnnb1 (Garcia-Rostan G et al. Cancer Res 1999, 59:1811). Our case further expands the histopathologic and molecular spectrum of this rare entity.

Progression of duodenal neoplasia to advanced adenoma in patients with familial adenomatous polyposis

BackgroundPatients with familial adenomatous polyposis (FAP) have a lifetime risk of developing duodenal adenomas approaching 100%, and the relative risk for duodenal cancer compared with the general population is high. We conducted a retrospective study to investigate the progression of non-ampullary duodenal adenomas (NADAs) and risk factors for advanced lesions in patients with FAP.MethodsOf 248 patients with 139 pedigrees at 2 institutes, we assessed 151 patients with 100 pedigrees with a pathogenic germline variant in the adenomatous polyposis coli gene, excluding mosaic variants. We evaluated the prevalence of NADAs in patients with FAP, the progression of these adenomas to advanced adenoma during the observation period, and the risk factors for the lifetime development of high-grade dysplasia (HGD), large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV.ResultsDuring the median observation period of 7 years, the incidences of patients with NADAs, with more than 20 polyps, with polyps ≥ 10 mm, with HGD, and with stage IV at the last esophagogastroduodenoscopy were increased 1.6-fold, 1.7-fold, 5-fold, 22-fold, and 9-fold, respectively. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period because we performed endoscopic intervention for advanced adenomas. Stage progression was observed in 71% of 113 patients. Stage IV was more common in women, patients with a history of colectomy, and those with a 3’ side mutation in their adenomatous polyposis coli gene.ConclusionsNADAs in patients with FAP frequently become exacerbated. Our findings suggest that patients with FAP who develop duodenal adenomas should be surveyed to prevent the development of duodenal cancer.

Interleukin-33 has the protective effect on oligodendrocytes against impairment induced by cuprizone intoxication

Our prior investigations have demonstrated the pivotal role of IL-33 in facilitating the maturation of oligodendrocytes (OLs), prompting our interest in exploring its potential therapeutic effects. In this study, our focus was directed towards deciphering the functions of interleukin-33 (IL-33) in established demyelinating mouse model induced by the feeding of cuprizone (CPZ)-containing diet. We observed the reduction in corpus callosal adenomatous polyposis coli (APC)+ OLs with IL-33 expression in mice subjected to CPZ feeding for durations of 6 and 8 weeks. In parallel, the levels of IL-33 in the corpus callosum declined after CPZ-containing diet. Furthermore, we conducted experiments utilizing primary oligodendrocyte precursor cells (OPCs) and mature OLs, which were exposed to CPZ. A decrease in the expression of myelin basic protein (MBP) was evident in the cultures of mature OLs after treatment with CPZ. Additionally, both IL-33 mRNA and protein levels exhibited downregulation. To counteract the diminished IL-33 levels induced by CPZ, we employed a lentiviral vector to overexpress IL-33 in OLs. Intriguingly, the overexpression of IL-33 (IL33OE) in OLs resulted in a more distinct membranous morphology following CPZ treatment when compared to that observed in OL Mock cultures. Moreover, MBP protein levels in the presence of CPZ were higher in IL33OE OLs than that detected in OL Mock cultures. These findings collectively indicate that IL-33 possesses the capability to mitigate CPZ-induced damage and bolster OL homeostasis. In summary, our study underscores the importance of IL-33 in the context of demyelinating diseases, shedding light on its potential therapeutic implications for fostering remyelination and preserving OL function.

MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density

BackgroundInherited defects in the base-excision repair gene MBD4 predispose individuals to adenomatous polyposis and colorectal cancer, which is characterized by an accumulation of C > T transitions resulting from spontaneous deamination of 5’-methylcytosine.MethodsHere, we have investigated the potential role of MBD4 in regulating DNA methylation levels using genome-wide transcriptome and methylome analyses. Additionally, we have elucidated its function through a series of in vitro experiments.ResultsHere we show that the protein MBD4 is required for DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a genome-wide hypomethylation of promoters, gene bodies and repetitive elements in the absence of MBD4 in vivo. Methylation mark loss is accompanied by a broad transcriptional derepression phenotype affecting promoters and retroelements with low methylated CpG density. MBD4 in vivo forms a complex with the mismatch repair proteins (MMR), which exhibits high bi-functional glycosylase/AP-lyase endonuclease specific activity towards methylated DNA substrates containing a G/T mismatch. Experiments using recombinant proteins reveal that the association of MBD4 with the MMR protein MLH1 is required for this activity.ConclusionsOur data identify MBD4 as an enzyme specifically designed to repair deaminated 5-methylcytosines and underscores its critical role in safeguarding against methylation damage. Furthermore, it illustrates how MBD4 functions in normal and pathological conditions.

Creation and beta testing of a "choose your own adventure" digital simulation to reinforce motivational interviewing skills in genetic counseling.

Standardized patients and/or role-playing are commonly used for practicing genetic counseling (GC) skills. Use of digital simulation, incorporating gamification elements, would require fewer resources to sustain than standardized patients. This manuscript reports steps taken and the lessons learned from creating a digital "Choose your own adventure" simulation in which students select preferred dialog for a genetic counselor who is seeing an adult patient to discuss genetic testing for the known pathogenic variant that caused familial adenomatous polyposis (FAP) in their father. The case has three endings, one of which is attained by selecting options that are mostly consistent with motivational interviewing counseling techniques. We conducted a preliminary evaluation of our beta version among nine GC students and one educator using a survey to assess acceptability and appropriateness as well as to elicit open-ended feedback. All participants agreed or strongly agreed with statements indicating the case was acceptable, appropriate, and fun. Users particularly appreciated the immediate feedback given throughout the case simulation. Many users wanted more options to select from and listed various other recommendations, including several which would require substantial resources to implement.

Region-specific Wnt signaling responses promote gastric polyp formation in patients with familial adenomatous polyposis.

Germline adenomatous polyposis coli (APC) mutation in patients with familial adenomatous polyposis (FAP) promotes gastrointestinal polyposis, including the formation of frequent gastric fundic gland polyps (FGPs). In this study, we investigated how dysregulated Wnt signaling promotes FGPs and why they localize to the corpus region of the stomach. We developed a biobank of FGP and surrounding nonpolyp corpus biopsies and organoids from patients with FAP for comparative studies. Polyp biopsies and polyp-derived organoids exhibited enhanced Wnt target gene expression. Polyp-derived organoids with intrinsically upregulated Wnt signaling showed poor tolerance to further induction, suggesting that high Wnt restricts growth. Targeted genomic sequencing revealed that most gastric polyps did not arise via APC loss of heterozygosity. Studies in genetic mouse models demonstrated that heterozygous Apc loss increased epithelial cell proliferation in the corpus but not the antrum, while homozygous Apc loss was not maintained in the corpus yet induced hyperproliferation in the antrum. Our findings suggest that heterozygous APC mutation in patients with FAP may be sufficient to drive polyp formation in the corpus region while subsequent loss of heterozygosity to further enhance Wnt signaling is not tolerated. This finding contextualizes the abundant yet benign nature of gastric polyps in FAP patient corpus compared with the rare, yet adenomatous polyps in the antrum.

Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process.

The introduction of premature termination codons (PTCs), as a result of splicing defects, insertions, deletions, or point mutations (also termed nonsense mutations), lead to numerous genetic diseases, ranging from rare neuro-metabolic disorders to relatively common inheritable cancer syndromes and muscular dystrophies. Over the years, a large number of studies have demonstrated that certain antibiotics and other synthetic molecules can act as PTC suppressors by inducing readthrough of nonsense mutations, thereby restoring the expression of full-length proteins. Unfortunately, most PTC readthrough-inducing agents are toxic, have limited effects, and cannot be used for therapeutic purposes. Thus, further efforts are required to improve the clinical outcome of nonsense mutation suppressors. Here, by focusing on enhancing readthrough of pathogenic nonsense mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, we show that disturbing the protein translation initiation complex, as well as targeting other stages of the protein translation machinery, enhances both antibiotic and non-antibiotic-mediated readthrough of nonsense mutations. These findings strongly increase our understanding of the mechanisms involved in nonsense mutation readthrough and facilitate the development of novel therapeutic targets for nonsense suppression to restore protein expression from a large variety of disease-causing mutated transcripts.

Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer.

The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92). Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

The Significance of Histopathological Findings on Clinical Outcomes in Endoscopic Papillectomy with Endocut

This study aimed to evaluate primary clinical outcomes in patients who underwent endoscopic papillectomy (EP) using the Endocut mode while examining the pathological characteristics of the margin of the resected specimen. To this end, 70 patients who underwent Endocut EP were included. Resection margins were classified according to pathological findings as “negative”, “positive”, or “uncertain (difficult pathological evaluation)”. The effect of pathological resection margins on residual tumor recurrence rates was evaluated. The median follow-up was 47 months (range, 22–84). Eleven patients (15.7%) were diagnosed with residual tumors, ten of whom were diagnosed within 6 months after EP. The resection margins were pathologically negative in 27 patients, positive in 15, and uncertain in 28; residual tumors occurred in 5 patients (33.3%) in the positive group, 5 (17.9%) in the uncertain group, and 1 (3.7%) in the negative group. The patient in the negative group had familial adenomatous polyposis (FAP). Female sex, FAP, and uncertain or positive resection margins were significantly more common in residual patients (p = 0.009, 0.044, and 0.041, respectively). Pathological resection margins can be used to infer the residual tumor incidence, leading to early post-treatment of residual tumors.

Salvage treatment for local recurrence after endoscopic resection for superficial nonampullary duodenal epithelial tumors

Background and AimsLocal recurrence is a significant concern in endoscopic resection of superficial nonampullary duodenal tumors (SNADTs). Our objective was to elucidate the clinical outcomes of salvage endoscopic treatment. MethodsThis retrospective study included consecutive patients who underwent endoscopic resection of SNADTs between January 2013 and December 2021. Four hundred thirty-three patients were observed, excluding those with familial adenomatous polyposis and those who did not undergo surveillance endoscopy. Local recurrence was defined as histologically proven adenoma or adenocarcinoma in contact with a prior endoscopic resection scar. The clinicopathological characteristics of patients with local recurrence and outcomes of salvage endoscopic treatment were evaluated. ResultsLocal recurrence occurred in 33 (8%) of the 433 patients after endoscopic resection for SNADT. Multivariate analysis identified older age (≥63 years), larger lesion size (≥13 mm), and piecemeal resection as significant independent predictors of local recurrence. Among the 33 patients with 33 recurrent lesions, 10 lesions (30%) disappeared after forceps biopsy. Three patients (9%) remained untreated. Sixteen lesions (48%) disappeared after one session of salvage endoscopic treatment, and four lesions (12%) disappeared after two sessions of treatment. Among these 24 treatment sessions, underwater endoscopic mucosal resection was performed in 19 sessions. The median post-procedural hospitalization period was four days (interquartile range, 3–4.25 days). Delayed bleeding occurred in three sessions. No recurrences have been detected in the 30 salvaged patients. The median recurrence-free survival time was 24.5 months (interquartile range, 14–48.75 months). ConclusionsLocal recurrence after endoscopic resection of SNADT can be managed endoscopically.

Risk for Hereditary Neoplastic Syndromes in Women with Mismatch Repair-Proficient Endometrial Cancer.

Endometrial cancer (EC) is a prevalent malignancy in women, and those who are proficient in the DNA mismatch repair (pMMR) pathway may have a family history (FH) that meets the criteria for a hereditary neoplastic condition (HNS). This study aimed to estimate the risk of HNS in women with pMMR endometrial tumors by analyzing their FH. To achieve this, we collaborated with a primary study and collected FH information by telephone. The final sample comprised 42 women who responded to the Primary Screening Questionnaire. Their family pedigrees were drawn and categorized according to internationally standardized criteria for the risk of HNS. Results showed that 26 women (61%) were found to be at risk for HNS, with Bethesda criteria being met by 23%, Amsterdam criteria by 15%, and 4% met the attenuated familial adenomatous polyposis criteria. Our results emphasize the importance of FH and the need to encourage healthcare professionals to collect and document FH more frequently, even if it is self-reported. By identifying individuals with HNS, we can improve their outcomes and reduce the burden of cancer in families with a predisposition to cancer.

Integrated genotype–phenotype analysis of familial adenomatous polyposis-associated hepatocellular adenomas

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by numerous colorectal adenomas. In addition, FAP patients may develop extraintestinal manifestations. Several cases of hepatocellular adenomas (HCA) detected accidentally in FAP patients have raised the so-far unsolved question of whether they represent a specific manifestation of FAP or a mere coincidence. To investigate the incidence of liver tumors in FAP patients, we analyzed our diagnostic database from 1991 to 2021. Among the 58 hepatic mass lesions identified, five HCAs occurring in three patients with FAP were identified, and comprehensive morphological, immunohistological, and molecular analysis employing targeted next-generation sequencing was conducted for characterization. The HCAs in this study showed no cytological or histological atypia. They displayed a diffuse, strong positivity for glutamine synthetase but no nuclear beta-catenin immunostaining. In two patients, the adenomas showed moderate immunoreactivity against serum amyloid A. Consistent with the diagnosis of FAP, molecular profiling revealed a pathogenic germline mutation of the APC gene in all analyzed adenomas as well as deleterious somatic second hits. All somatic mutations were localized between codons 1345 and 1577. No mutations were found in the catenin beta 1 gene. HCA in FAP patients can be a specific, although rare, neoplastic manifestation of this inborn disease and represents a distinct subgroup of HCAs. These benign tumors represent an important differential diagnosis for hepatic metastases in FAP patients and require adequate clinical and molecular (diagnostic) assessments for optimal patient guidance.

Сomplications and functional outcomes after restorative proctocolectomy with ileal pouch–anal anastomosis in children: A single-center experience

BACKGROUND: Restorative proctocolectomy with ileal pouchanal anastomosis is a prominent treatment for adult patients with ulcerative colitis and familial adenomatous polyposis, with satisfactory functional outcomes. In literature, that technique in pediatric practice is described; however, in the domestic literature, there is no mention of ileal pouchanal anastomosis in children.&#x0D; AIM: This study aimed to examine the outcomes of ileal pouchanal anastomosis in pediatric patients.&#x0D; MATERIALS AND METHODS: The study comprised 33 patients with an ileal pouchanal anastomosis between January 2019 and June 2023. At the time of the ileal pouchanal anastomosis, the average age was 13 (5) yr. Patients were followed for an average of 17 (14) months.&#x0D; RESULTS: Patients with ulcerative colitis underwent three-stage surgical interventions more often than patients with another diagnosis (90% vs. 4%, p 0.0001), and the mean duration of surgery in ulcerative colitis patients was shorter than in patients with polyposis syndromes or total agangliosis: 173 (57) min versus 280 (73) min. Late complications were reported in five (15%) patients undergoing ileal pouchanal anastomosis. After the ileal pouchanal anastomosis, analysis of patient questionnaires revealed that children had satisfactory functional results.&#x0D; CONCLUSIONS: Several encouraging studies have confirmed good functional outcomes after ileal pouchanal anastomosis. Our findings suggest that ileal pouchanal anastomosis in children is associated with favorable results.

BMAP-27 Peptide Reduces Proliferation and Increases Apoptosis in Primary and Metastatic Colon Cancer Cell Lines

BMAP-27 peptide is reported to possess apoptotic and anti-proliferative effects against cancer cells but the actual mechanism of action is yet to be investigated. In the current investigation, we aimed to study the role of the BMAP-27 peptide in reducing proliferation and increasing apoptosis in colon cancer cell lines. In this study, we used primary and metastatic colon cancer cell lines SW480 and SW620. Cell proliferation was measured using MTT and CCK-8 assays, and cellular damage was analyzed by lactate dehydrogenase assay. Apoptosis, cell cycle, and proliferation potentials were measured by the expression of CASPASE3, BAX, BCL-2, TP53, CDK-6, PCNA, WNT11, AXIN1, and CTNNB1 genes. Additionally, in-silico studies were conducted to determine the binding affinities of BMAP-27 with adenomatous polyposis coli (APC) and β-catenin proteins, one of the primary regulators of colon cancer. BMAP-27 peptide reduced colon cancer cell proliferation, upregulated tumor suppressor genes CASPASE3, BAX, TP53, AXIN1 expression, and downregulated the expression of oncogenes BCL-2, CDK-6, PCNA, WNT11, CTNNB1 in both the cell lines, however, in the primary colon cancer cell line the changes are found to be more significant. The molecular dynamic simulation analysis revealed substantial binding affinity of the peptide to APC and β-catenin proteins. BMAP-27 peptide significantly inhibited the proliferation and induced apoptosis in the primary colon cancer cell line than in the metastatic colon cancer cell line. In-silico results suggest that BMAP-27 shows a strong binding affinity with APC and β-catenin proteins, highlighting its role in inhibiting colon cancer cell proliferation.

Gastric Polyps in Familial Adenomatous Polyposis Portuguese Patients: The First Western Cohort with Asian Features

Introduction: Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter pylori (HP) infection in Portugal, we aim to characterize GP in a series of Portuguese patients. Methods: In a retrospectively selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis. Results: Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA), and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA), and three foveolar-type GA (fovGA). IntGA were larger (60% >7 mm, p = 0.03), occurred predominantly in the distal stomach (66.7%, p = 0.024), in patients harboring gastric intestinal metaplasia (IM) (86.7%, p < 0.001), and duodenal adenomas (86.7%, p < 0.001). Conclusion: This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP >7 mm in the distal stomach and in patients harboring gastric intestinal metaplasia/duodenal adenomas should be considered.