Search Results (75)

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article

Cutaneous manifestations can serve as early and sometimes the first clinical indicators in various hereditary cancer predisposition syndromes. This review provides a comprehensive overview of the dermatological signs associated with these syndromes, aiming to facilitate their recognition in clinical practice. Hereditary Breast and Ovarian Cancer syndrome is notably linked to an increased risk of melanoma. BAP1 tumor predisposition syndrome is characterized by BAP1-inactivated melanocytic tumors. Muir–Torre syndrome, a variant of Lynch syndrome, presents with distinctive cutaneous neoplasms such as sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas. PTEN hamartoma tumor syndrome commonly features hamartomatous growths, trichilemmomas, acral keratoses, oral papillomas, and genital lentiginosis. Gorlin syndrome is marked by basal cell carcinomas and palmoplantar pits, while Peutz–Jeghers syndrome is identified by mucocutaneous pigmentation. In familial adenomatous polyposis, the cutaneous findings include epidermoid cysts, fibromas, desmoid tumors, and lipomas. Additionally, we examined monogenic disorders associated with cancer risk and skin involvement, such as xeroderma pigmentosum, neurofibromatosis type 1, familial atypical multiple-mole melanoma syndrome, and Fanconi anemia. The early recognition of these dermatologic features is essential for a timely diagnosis and the implementation of appropriate surveillance strategies in individuals with hereditary cancer syndromes. Full article

Ampullary adenomas are rare outgrowths at the ampulla of Vater that may progress into cancer via the adenoma-to-carcinoma sequence, particularly in individuals with hereditary polyposis syndrome. Many are diagnosed incidentally or once the lesion becomes large enough to cause obstruction. Traditionally managed surgically with high morbidity and mortality, advances in imaging and therapy have made endoscopic ampullectomy the first-line treatment for noninvasive lesions. Despite its high success rate and favorable safety profile, complications such as pancreatitis, ductal stenosis, bleeding, recurrence, and perforation can occur. Recommendations for optimal endoscopic techniques and surveillance intervals are largely based on expert opinion in interventional endoscopy and findings from small-scale studies. This review provides an updated framework for the diagnosis and management of ampullary adenomas. Full article

Familial adenomatous polyposis (FAP) is the most common hereditary colorectal adenomatous polyposis and cancer syndrome which has historically been associated with a near absolute risk of colorectal cancer. However, the morbidity and mortality from colorectal cancer has been greatly diminished by pre-symptomatic genetic testing which identifies affected individuals and by appropriately timed, risk-reducing surgery of the colorectum. Following colorectal surgery, cancer risk beyond the retained rectum or ileal pouch includes other gastrointestinal organs, especially those of the upper gastrointestinal tract. While genotype–phenotype correlations exist for the severity of colonic polyposis, they have not been demonstrated for upper gastrointestinal tract manifestations. We reviewed the impact of ethnicity on the upper gastrointestinal manifestations of FAP by a comparison of published data in patients with FAP from Asian and Western countries. Our main findings demonstrate that following risk-reducing surgery to mitigate colorectal cancer risk, patients with FAP remain at increased risk for upper gastrointestinal polyposis and cancer. The duodenal and gastric phenotype differs between patients with FAP from the West and the East, and all should be followed in a multidisciplinary surveillance program. Following risk-reducing surgery to mitigate colorectal cancer risk, patients with familial adenomatous polyposis remain at increased risk for upper gastrointestinal polyposis and cancer. The duodenal and gastric phenotype differs between patients with FAP from the West and the East, and all should be followed in a multidisciplinary surveillance program. Full article

The integrity of the genome is maintained by mismatch repair (MMR) proteins that recognize and repair base mismatches and insertion/deletion errors generated during DNA replication and recombination. A defective MMR system results in genome-wide instability and the progressive accumulation of mutations. Tumors exhibiting deficient MMR (dMMR) and/or high levels of microsatellite instability (termed “microsatellite instability high”, or MSI-H) have been shown to possess fundamental differences in clinical, pathological, and molecular characteristics, distinguishing them from their “microsatellite stable” (MSS) counterparts. Molecularly, they are defined by a high mutational burden, genetic instability, and a distinctive immune profile. Their distinct genetic and immunological profiles have made dMMR/MSI-H tumors particularly amenable to treatment with immune checkpoint inhibitors (ICIs). The ongoing development of biomarker-driven therapies and the evaluation of novel combinations of immune-based therapies, with or without the use of conventional cytotoxic treatment regimens, continue to refine treatment strategies with the goals of maximizing therapeutic efficacy and survival outcomes in this distinct patient population. Moreover, the resultant knowledge of the mechanisms by which these features are suspected to render these tumors more responsive, overall, to immunotherapy may provide information regarding the potential optimization of this therapeutic approach in tumors with proficient MMR (pMMR)/MSS tumors. Full article

Aim: Endo-Wing™ is a soft silicone device with six wing-like projections attached at the end of the colonoscope that provides superior visualization by flattening the colonic fold and helps to maintain a central view of the colonoscope during withdrawal. This study aims to compare the adenoma detection rate (ADR) between standard colonoscopy and Endo-Wing™-assisted colonoscopy. Methods: This is a single-center, single-blind, parallel-group, randomized, actively controlled, exploratory clinical trial conducted between July 2019 and April 2020. Participants aged 45 and above who were symptomatic of colorectal cancer (CRC) or with a history of adenoma and under active surveillance were included. Exclusion criteria included colonic strictures, tumors, active colitis, a previous history of polyposis syndrome, colostomy/ileostomy, or a BPPS score of 0. Participants were subsequently randomized to receive standard colonoscopy (n = 96) or Endo-Wing™-assisted colonoscopy (n = 96) at a 1:1 ratio using a central block randomization method with varying block sizes. The primary endpoint was the ADR, and the differences between the two groups were evaluated using univariable statistical methods. Results: The ADR, the number of adenomas, and the size of adenomas in the Endo-Wing™-assisted colonoscopy group were significantly higher compared to standard colonoscopy (p = 0.005, 0.035, and 0.035, respectively). Cecal intubation rates were similar in both groups (p > 0.999). The proportions of colonoscopy requiring increased sedation and standard sedation were similar in both groups (p = 0.613). No adverse effects of bleeding, perforation, and device dislodgement were reported in both groups. Conclusions: This study concludes that Endo-Wing™-assisted colonoscopy improves the ADR compared to standard colonoscopy. Full article

Background: Pancreatic cancer (PC) is among the deadliest types of cancer globally. While early detection helps avert adverse outcomes, screening is only recommended for individuals at high risk, specifically those with familial and/or genetic predispositions. The objectives of this study are to systematically review primary studies on the cost-effectiveness of PC screening and to identify the critical factors that influence cost-effectiveness. Methods: This systematic review was performed using PRISMA guidelines. Economic evaluation studies on PC screening were identified from searches on the SCOPUS and PubMed databases. The quality of reporting of the selected articles was assessed according to CHEERS 2022. Using predefined inclusion and exclusion criteria, two reviewers conducted the title–abstract review, full-text review, and data extraction to select relevant articles. The authors’ consensus was used to settle disagreements. The primary outcome was the incremental cost-effectiveness ratio, measured by cost per quality-adjusted life year and cost per life year saved. Results: Nine studies were selected for the final review. Most studies demonstrated that one-time screening for PC among high-risk individuals was cost-effective compared with no screening, while others found annual screening to also be cost-effective. High-risk was generally defined as having a >5% lifetime risk of PC and included individuals with either familial pancreatic cancer (FPC) or genetic susceptibility syndromes such as Peutz–Jeghers Syndrome, hereditary pancreatitis, hereditary non-polypoid colorectal cancer syndrome, familial adenomatous polyposis, and BRCA2 mutations. Individuals with new-onset diabetes (NOD) were also considered high-risk. Screening using mainly endoscopic ultrasound was cost-effective among FPC individuals and those with genetic syndromes. Risk-based screening was also cost-effective among patients with NOD. Conclusion: Screening for PC is cost-effective among selected high-risk individuals. However, cost-effectiveness depends on epidemiological factors, cost, the diagnostic performance of screening tools, and the overall design of studies. Full article

Lynch syndrome (LS)—also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC)—is caused by pathogenic germline mutations in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. Although it accounts for only 1–5% of all colorectal cancers (CRCs), LS presents with a particularly high lifetime cancer risk and often occurs at younger ages. Identifying LS in patients under 60 years old is crucial for targeted surveillance and early interventions. Variations in clinical presentation and prognosis may exist based on the specific gene mutated, yet these patterns are not fully elucidated. This review aims to synthesize data on clinical outcomes among LS patients under 60, with an emphasis on how different MMR gene mutation patterns might influence prognosis, survival, and treatment decisions. Five population-based studies examining CRC patients younger than 60 years were included according to predefined eligibility criteria. Two independent reviewers screened and extracted data focusing on MMR deficiency detection methods (microsatellite instability [MSI] and/or immunohistochemistry [IHC]), rates of confirmed germline mutations, frequency of BRAF testing, and clinical endpoints such as stage distribution, survival outcomes, and recurrence. Risk of bias was assessed using standardized tools appropriate to each study design. The synthesis focused on comparing outcomes among individuals with MLH1, MSH2, MSH6, and PMS2 mutations, as well as delineating the proportion of patients with sporadic MSI under 60 years of age. Across the five studies, MSI positivity in CRC patients under 60 years ranged from 7.5% to 13%. The frequency of confirmed germline MMR mutations varied between 0.8% and 5.2% in specific cohorts, aligning with LS prevalence estimates of 1–5%. Different mutation patterns correlated with some variation in clinical presentation. Cases with MSH2 and MLH1 mutations more frequently exhibited synchronous or metachronous tumors, while MSH6 and PMS2 mutations displayed more heterogeneous IHC patterns. Where survival data were provided, LS patients under 60 years had better overall survival compared to MMR-proficient individuals, though some studies also noted a potential lack of benefit from standard 5-fluorouracil adjuvant therapy in MMR-deficient tumors. Screening by MSI or by IHC—supplemented with BRAF mutation testing to exclude sporadic MSI—facilitates early detection of LS in CRC patients under 60 and highlights notable differences between mutation types. Although overall outcomes for LS patients can be favorable, especially for stage II disease, the precise impact of each specific mutated gene on clinical course remains heterogeneous. Future large-scale prospective studies are needed to clarify optimal screening protocols and individualized treatment strategies for LS patients under 60. Full article

Background: Hereditary colorectal cancer syndromes, including familial adenomatous polyposis (FAP), Lynch syndrome (LS), and Peutz–Jeghers syndrome (PJS), are associated with an increased risk of small bowel cancer (SBC). Due to the low incidence and non-specific presentation of SBC, effective surveillance strategies are essential for early detection and management. This review aims to evaluate and compare current endoscopic techniques for small bowel surveillance in these patients. Methods: A comprehensive review was conducted using peer-reviewed studies sourced from PubMed. Various endoscopic modalities, including capsule endoscopy (CE), device-assisted enteroscopy (DAE), and intraoperative enteroscopy (IOE), were assessed for their diagnostic yield, safety, and clinical utility. Surveillance recommendations of the different syndromes were also examined. Results: CE offers high sensitivity but lacks histological sampling capability. DAE, including double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE), enables direct visualization, biopsy, and therapeutic interventions, albeit with greater procedural complexity. In FAP, duodenal surveillance follows the Spigelman classification to stratify cancer risk, while jejunal and ileal polyps remain less studied. LS patients have an increased SBC risk, warranting tailored endoscopic approaches. In PJS, surveillance aims to mitigate intussusception risks and allow early malignancy detection. Conclusions: Optimized surveillance strategies in hereditary colorectal cancer syndromes require a multimodal approach, integrating advanced endoscopic techniques with genetic risk stratification. Centralized care in tertiary centers improves outcomes by ensuring standardized surveillance protocols and enhancing early cancer detection. Artificial intelligence (AI) applied to CE and DAE is shaping promising prospects for the future surveillance of small bowel polyps by enhancing diagnostic accuracy and reducing the duration of the diagnostic process. Further research should investigate AI-assisted imaging and molecular biomarkers to optimize screening strategies. Full article

Hepatoblastoma (HB) is the most common malignant liver tumor in children under five years of age. Although globally rare, it accounts for a large proportion of liver cancer in children and has poor survival rates in high-risk and metastatic cases. This review discusses the molecular mechanisms, diagnostic methods, and therapeutic strategies of HB. Mutations in the CTNNB1 gene and the activation of the Wnt/β-catenin pathway are essential genetic factors. Furthermore, genetic syndromes like Beckwith–Wiedemann syndrome (BWS) and Familial Adenomatous Polyposis (FAP) considerably heighten the risk of associated conditions. Additionally, epigenetic mechanisms, such as DNA methylation and the influence of non-coding RNAs (ncRNAs), are pivotal drivers of tumor development. Diagnostics include serum biomarkers, immunohistochemistry (IHC), and imaging techniques. Standard treatments are chemotherapy, surgical resection, and liver transplantation (LT). Emerging therapies like immunotherapy and targeted treatments offer hope against chemotherapy resistance. Future research will prioritize personalized medicine, novel biomarkers, and molecular-targeted therapies to improve survival outcomes. Full article

Background: The efficacy of germline testing in colorectal cancer has been proven; however, germline testing in individuals with sebaceous neoplasms is less well defined. This review aims to summarize the literature on sebaceous neoplasms to date, describing the somatic tumor profiles, tumor screening methods, and personal and family history that are suspicious of a germline mutation. Sebaceous neoplasms can be attributed to a variety of etiologies, including UV exposure, immunodeficiency, germline mutations, or multifactorial influences associated with aging. Sebaceous tumors with abnormal microsatellite instability and mismatch repair deficiency are indicative of a germline mutation in 20–50% of cases, which is similar to rates found in colorectal tumors. Personal and familial history can also be suggestive of a germline etiology in these patients and should be assessed routinely, as approximately 30% of individuals with sebaceous neoplasms carry a germline mutation. We outline a strategy for the identification of individuals at risk for germline mutations, recommendations for the management of mutation carriers, and treatment options for individuals with sebaceous neoplasms. Conclusions: Sebaceous tumors are most often sporadic; however, evaluations of a germline etiology are prudent to effectively identify those at risk of additional malignancies as well as at-risk family members. Referral to genetic counseling and germline genetic testing for individuals at risk can significantly impact cancer treatment and screening in patients and their families. Full article

Nasal cytology is a non-invasive, affordable, and easily executable technique commonly used in research to study rhinitis and, to a lesser extent, chronic rhinosinusitis. It is particularly useful for the differential diagnosis of non-allergic rhinitis and for phenotyping chronic rhinosinusitis. Allergic rhinitis, asthma, and aspirin intolerance are frequent comorbidities of chronic rhinosinusitis. A diagnostic system has been proposed to assess the severity of chronic rhinosinusitis (clinical-cytological grading), incorporating nasal cytology and comorbidity observation. This score correlates with the recurrence risk of chronic rhinosinusitis with nasal polyposis. Specifically, a higher grade is often linked to asthma, aspirin intolerance, a recurrent disease requiring surgery, and a mixed cell phenotype (eosinophilic and mast cell). Although nasal cytology has been shown to be able to replace bronchial analysis with acceptable precision due to its technical characteristics, its use in diseases affecting both upper and lower airways remains limited. The main limitation of this technique is its lack of standardization, which currently hinders its widespread clinical adoption despite its increasing familiarity among allergists and otolaryngologists. In the context of the unitary airways hypothesis, nasal cytology could also provide valuable insights for managing lower airway diseases like chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, which significantly impact quality of life and healthcare costs. This review aims to provide an overview of nasal cytology, highlighting its limitations and potential applications in chronic respiratory diseases. Full article

Background: Colorectal cancer (CRC) is the second leading cause of cancer death in Kuwait. The effectiveness of colonoscopy in preventing CRC is dependent on a high adenoma detection rate (ADR). Computer-aided detection can identify (CADe) and characterize polyps in real time and differentiate benign from neoplastic polyps, but its role remains unclear in screening colonoscopy. Methods: This was a randomized-controlled trial (RCT) enrolling patients 45 years of age or older presenting for outpatient screening or surveillance colonoscopy (Kuwait clinical trial registration number 2047/2022). Patients with a history of inflammatory bowel disease, alarm symptoms, familial polyposis syndrome, colon resection, or poor bowel preparation were excluded. Patients were randomly assigned to either high-definition white-light (HD-WL) colonoscopy (standard of care) or HD-WL colonoscopy with the CADe system. The primary outcome was ADR. The secondary outcomes included polyp detection rate (PDR), adenoma per colonoscopy (APC), polyp per colonoscopy (PPC), and accuracy of polyp characterization. Results: From 1 September 2022 to 1 March 2023, 102 patients were included and allocated to either the HD-WL colonoscopy group (n = 51) or CADe group (n = 51). The mean age was 52.8 years (SD 8.2), and males represented 50% of the cohort. Screening for CRC accounted for 94.1% of all examinations, while the remaining patients underwent surveillance colonoscopy. A total of 121 polyps were detected with an average size of 4.18 mm (SD 5.1), the majority being tubular adenomas with low-grade dysplasia (47.1%) and hyperplastic polyps (46.3%). There was no difference in the overall bowel preparation, insertion and withdrawal times, and adverse events between the two arms. ADR (primary outcome) was non-significantly higher in the CADe group compared to the HD colonoscopy group (47.1% vs. 37.3%, p = 0.3). Among the secondary outcomes, PDR (78.4% vs. 56.8%, p = 0.02) and PPC (1.35 vs. 0.96, p = 0.04) were significantly higher in the CADe group, but APC was not (0.75 vs. 0.51, p = 0.09). Accuracy in characterizing polyp histology was similar in both groups. Conclusions: In this RCT, the artificial intelligence system showed a non-significant trend towards improving ADR among Kuwaiti patients undergoing screening or surveillance colonoscopy compared to HD-WL colonoscopy alone, while it significantly improved the detection of diminutive polyps. A larger multicenter study is required to detect the true effect of CADe on the detection of adenomas. Full article

Hereditary polyposis syndromes are rare but potentially devastating conditions which require multidisciplinary care from an early age. Societal guidelines, which ideally combine expert opinions and medical evidence, serve as the framework for disease diagnosis, surveillance and treatment. However, there is a significant underrepresentation of pediatric gastroenterology input in guideline formulation, and additionally, recommendations can vary significantly between societies, which can have a moderate-to-high clinical impact on patient care. This paper aims to summarize key differences in management based on societal guidelines and identify some of the factors which may contribute to divergence in care in hereditary polyposis syndromes in pediatric patients. The authors review the literature underlying the divergence in recommendations and attempt to reconcile these differences with a closer consideration of the pediatric population, considering the available evidence. This review highlights the need to harmonize recommendations across subspecialties and professional societies and sheds light on the significant underrepresentation of pediatric gastroenterology input in guideline formulation. Given the poor-quality evidence underlying many societal guidelines and the lack of pediatric gastroenterology representation in guideline formulation in these rare syndromes, there is a need for collaborative, multicenter, registry-based studies to refine and improve care standards. Full article

Bardet–Biedl syndrome (BBS) is a genetic disease caused by mutations of the BBS genes that encode proteins involved in cilia functioning. It can present with major and/or minor clinical manifestations, such as rod–cone dystrophy, polydactyly, obesity, speech delay, anosmia, congenital heart disease and genital and renal abnormalities. Diagnosis of this rare disease is based on clinical criteria and can be confirmed with molecular genetic testing. Although BBS is a ciliopathy, nasal polyposis has never before been reported in patients with this condition. This article presents the case of a 12-year-old male patient admitted with symptoms of retinopathy, development delay, anosmia, bifid epiglottis and recurrent nasal polyposis. After several clinical, imaging and genetic examinations, the patient was diagnosed with BBS. His nasal symptoms were treated with functional endoscopic sinus surgery and long-term antibiotic therapy, whereas courses of topical antibiotics as well as topical and systemic corticosteroids had no effect. As a conclusion, it is a rare case that presents new clinical manifestations (nasal polyps) that can be related to BBS and possible effective treatments. Full article