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Irish Journal of Medical Science Apr 2023Desmoid tumours are benign fibromatous tumours arising from dysregulated myofibroblast proliferation within musculoaponeurotic structures. They can occur sporadically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Desmoid tumours are benign fibromatous tumours arising from dysregulated myofibroblast proliferation within musculoaponeurotic structures. They can occur sporadically but more commonly are associated with genetic syndromes such as familial adenomatous polyposis (Sakorafas et al. in Surg Oncol 16(2):131-142, 2007) (FAP). Mutations in either the Wnt, β-catenin or APC genes are 'key' triggers for the development of these tumours (Howard and Pollock in Oncol Ther 4(1):57-72, 2016). Classically, these tumours do not metastasise; however, they are associated with significant morbidity and mortality due to their infiltrative pattern and/or local invasion. Historically, surgical resection was the cornerstone of treatment. There remains paucity of data regarding outcomes following the surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity.
OBJECTIVES
The aim of this review was to assess the current evidence for surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity.
METHODS
A systematic search of articles in PubMed, EMBASE and The Cochrane Library databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the period from January 2000 to November 2020.
RESULTS
Twenty-three studies were included, of which, 749 patients had surgical resection (696 for primary and 53 for recurrent desmoids), 243 patients (18.8%) were medically managed and 353 patients (27.3%) underwent surveillance. Median follow-up was 51.4 months (range 1-372). Six-hundred and ninety-six of the 749 resections (92.9%) underwent primary desmoid resection, with the remaining 53 (7.1%) undergoing resection for recurrence. One-hundred and two surgically managed patients (19%) developed a (re)recurrence, with mesenteric involvement the commonest site for recurrence (55%). When comparing recurrence post-surgery to progression following medical therapy, there was a trend towards better outcomes with surgery, with 25% of surgical patients having a recurrence versus 50.5% having progression with medical therapy [OR 0.40 (95% CI 0.06-2.70), p = 0.35]. Major morbidity following surgery was 4.4% (n = 33) with 2% (n = 14) mortality within 30 days of resection.
CONCLUSION
The management of desmoids has considerable heterogeneity. Surgical resection for abdominal desmoids remains a valid treatment option in highly selective cases where negative margins can be obtained, with low major morbidity and/or mortality.
Topics: Humans; Fibromatosis, Aggressive; Fibromatosis, Abdominal; Adenomatous Polyposis Coli; Mutation; Colectomy
PubMed: 35445926
DOI: 10.1007/s11845-022-03008-8 -
Techniques in Coloproctology Sep 2022Ileal pouch-anal anastomosis (IPAA) is commonly used to restore gastrointestinal continuity after surgical treatment of mucosal ulcerative colitis (MUC) and familial... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of the outcome of ileal pouch-anal anastomosis in patients with ulcerative colitis versus patients with familial adenomatous polyposis.
BACKGROUND
Ileal pouch-anal anastomosis (IPAA) is commonly used to restore gastrointestinal continuity after surgical treatment of mucosal ulcerative colitis (MUC) and familial adenomatous polyposis (FAP). The aim of the present systematic review was to compare the outcomes of patients with MUC and patients with FAP who underwent IPAA.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review was performed. PubMed, Scopus, and Web of Science were searched through December 2021. Cohort and randomized studies were eligible for inclusion if they directly compared patients with MUC and FAP who underwent IPAA. The main outcome measures were pouch failure, complications, and need for pouch excision or revision. ROBINS-I tool was used to assess the risk of bias across the studies. A random-effect meta-analysis was conducted.
RESULTS
Twenty-three studies (9200 patients) were included in this meta-analysis. Seven thousand nine hundred fifty (86.4%) had MUC and 1250 (13.6%) had FAP. The median age of patients was 33.1 years. The male to female ratio was 1.4:1. MUC had higher odds of pouchitis (OR 3.9, 95% CI 2.8-5.4, p < 0.001), stricture (OR 1.82, 95% CI 1.25-2.65, p = 0.002), fistula (OR 1.74, 95% CI 1.18-2.54, p = 0.004), and total complications (OR 1.89, 95% CI 1.3-2.77, p < 0.001) as compared to FAP. Both groups had similar odds of pelvic sepsis, leakage, pouch failure, excision, revision, and fecal incontinence.
CONCLUSIONS
Although patients with MUC undergoing IPAA may be at a higher risk of developing complications, particularly pouchitis, stricture, and fistula; the ultimate and functional outcome of the pouch is similar to patients with FAP. Pouch failure, excision and revision were similar in the two groups.
Topics: Adenomatous Polyposis Coli; Adult; Anastomosis, Surgical; Colitis, Ulcerative; Colonic Pouches; Constriction, Pathologic; Female; Humans; Male; Postoperative Complications; Pouchitis; Proctocolectomy, Restorative; Retrospective Studies; Treatment Outcome
PubMed: 35357610
DOI: 10.1007/s10151-022-02617-w -
Clinical Ophthalmology (Auckland, N.Z.) 2022Familial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of... (Review)
Review
Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) as a Screening Marker for Familial Adenomatous Polyposis (FAP): Systematic Literature Review and Screening Recommendations.
PURPOSE
Familial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a highly specific phenotypical marker for FAP that can be used in screening at-risk individuals. Screening recommendations including morphological subclassification were formulated with supporting literature.
METHODS
A systematic literature review with a comprehensive search strategy was conducted using online databases. Manual searches of bibliographies and reference lists were also performed. Studies meeting inclusion criteria were graded with respect to their hierarchy of evidence and strength of recommendations according to the National Health and Medical Research Council (NHMRC) guidelines of Australia.
RESULTS
Almost 4500 participants were analysed across 28 included studies. The mean specificity of CHRPE as a phenotypical screening marker of FAP was 89% (standard deviation (SD); 14) with a mean sensitivity of 79% (SD; 8). The mean prevalence of CHRPE amongst FAP participants; at-risk participants were found to be 76% (SD; 24) and 37% (SD; 21) respectively. Bilateralism and multiple lesion number ≥3 are features highly specific for FAP.
CONCLUSION
CHRPE was found to be a non-invasive, rapid, early phenotypical screening marker of FAP. Clinical recognition further allows increased gene analysis efficiency. The absence of CHRPE alone cannot exclude FAP. Our screening recommendations provide guidance to clinicians on evidence based CHRPE assessment. We would advocate inclusion of ocular examinations as part of a three-pronged approach, along with endoscopy and genetic testing, for efficient, timely FAP assessment in at-risk individuals.
PubMed: 35321042
DOI: 10.2147/OPTH.S354761 -
Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review.Familial Cancer Oct 2022Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or... (Review)
Review
Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.
Topics: Female; Humans; Middle Aged; Adenoma; Adenomatous Polyposis Coli; Breast Neoplasms; Colorectal Neoplasms; Deoxyribonuclease (Pyrimidine Dimer); Genetic Predisposition to Disease; Germ-Line Mutation; Male; Adult; Aged
PubMed: 35292903
DOI: 10.1007/s10689-022-00291-3 -
Journal of the European Academy of... Jun 2022Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be... (Review)
Review
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be managed with topical treatments, moderate-to-severe forms require systemic therapies. Dupilumab is the first human monoclonal antibody approved for the treatment of AD. Its action is through IL-4 receptor alpha subunit inhibition, thus blocking IL-4 and IL-13 signaling pathways. It has been shown to be an effective, well-tolerated therapy for AD, as well as for asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and eosinophilic esophagitis (EoE). However, an increasing incidence of dupilumab-induced ocular surface disease (DIOSD) has been reported in patients treated with dupilumab, as compared to placebo. The aim of this study was to summarize scientific data regarding DIOSD in AD patients treated with dupilumab. A search of PubMed and clinicaltrials.gov databases was performed. There was no limit to study design. All AD cases were moderate-to-severe. DIOSD was either dermatologist-, allergist-, or ophthalmologist-assessed. Evidence shows that DIOSD occurs most frequently in patients with atopic dermatitis and not in other skin conditions, neither in patients with asthma, CRSwNP, nor EoE who are on dupilumab treatment. Further studies are warranted in order to establish a causal relationship between dupilumab and ocular surface disease. Nevertheless, ophthalmological evaluations prior to dupilumab initiation can benefit AD patients with previous ocular pathology or current ocular symptomatology. Also, patch testing for ocular allergic contact dermatitis might be advantageous in patients with a history of allergic conjunctivitis. Furthermore, TARC, IgE, and circulating eosinophils levels might be important biomarkers for a baseline assessment of future candidates to dupilumab treatment. However, TARC measurements should be resumed for research purposes only.
Topics: Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Humans; Interleukin-4 Receptor alpha Subunit; Severity of Illness Index; Treatment Outcome
PubMed: 35122335
DOI: 10.1111/jdv.17981 -
The Journal of Craniofacial Surgery Jun 2022Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease characterized by a variety of inflammatory mechanisms. Extensive genetic analyses have shown that among...
The Effect of the Premedication with Systemic Corticosteroids and Antibiotics on Inflammation and Intraoperative Bleeding During Sinonasal Endoscopic Surgery for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).
INTRODUCTION
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease characterized by a variety of inflammatory mechanisms. Extensive genetic analyses have shown that among the molecules that are involved in its genetic base, interleukins (ILs) play a critical role in the development and progression of CRSwNP. ILs, such us IL-4 (5q31.1), IL-5 (5q31.1), IL-13 (5q31.11), and IL-25 (14q11.2) are found to be overexpressed.
PURPOSE
Our aim is to investigate, through a systemic review, the effect of the premedication with systemic corticosteroids and antibiotics on inflammation and intraoperative bleeding during sinonasal endoscopic surgery for CRSwNP.
MATERIALS AND METHODS
The search period covered January 1979 to February 2021, using the scientific databases PubMed, Scien-ceDirect, Scopus, Cochrane Library και Google Scholar. Search terms were "effect, premedication, systemic corticosteroids, antibiotics, intraoperative, bleeding, inflammation, sinonasal, endoscopic surgery, chronic rhinosinusitis, and nasal polyposis."
RESULTS
From an initial 80 titles found in the above medline databases, the evaluations led to the final inclusion of 15 papers. Eighty titles found in the above medline databases. Eleven titles were excluded as they did not include a summary and full text in English language. Sixty-nine titles collected and duplicate references were searched. Twelve titles were excluded due to double reporting. Fifty-seven articles remained for systematic review. Fourty-two articles were excluded after systematic review and correlation with the research field. Fifteen articles were eventually included in the literature review.
CONCLUSIONS
The effect of corticosteroids and antibiotics on the size of nasal polyps, nasal symptoms, and systemic markers of inflammation is significant. Each of the above factors acts on different pathogenetic inflammatory mechanisms.The use of perioperative corticosteroids reduces blood loss and operation time and improves the quality of the surgical field. There are no other medications that have been shown to improve the surgical field and outcome. Whether there is an additive effect on systemic corticosteroids on top of nasal corticosteroids is unclear. The european position paper on rhinosinusitis and nasal polyps steering group advises to use (nasal) corticosteroids before endoscopic sinus surgery.However, it should be considered in future studies whether some minor differences are due to differences in the initial doses of corticosteroids or during treatment in the preoperative period. It is worth mentioning that although high doses of corticosteroids are required to control the progression of rhinosinusitis with nasal polyps, the optimal initial dosage and the total duration of the treatment have not yet been standardized in patients with CRSwNP and future studies are required to determine the 2 above parameters (optimal dosage and duration of treatment). There are, therefore, known risks from corticosteroid administration, and clinicians should consider them when evaluating each patient. Each patient should be considered as an individual case with individualized treatment.
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Chronic Disease; Humans; Inflammation; Nasal Polyps; Premedication; Rhinitis; Sinusitis; Steroids
PubMed: 35093993
DOI: 10.1097/SCS.0000000000008285 -
Familial Cancer Oct 2022Desmoid tumours (DT) are one of the main causes of death in patients with familial adenomatous polyposis (FAP). Surgical trauma is a risk factor for DT, yet a colectomy... (Meta-Analysis)
Meta-Analysis Review
Desmoid tumours (DT) are one of the main causes of death in patients with familial adenomatous polyposis (FAP). Surgical trauma is a risk factor for DT, yet a colectomy is inevitable in FAP to prevent colorectal cancer. This systematic review and meta-analysis aimed to synthesize the available evidence on DT risk related to type, approach and timing of colectomy. A search was performed in MEDLINE, EMBASE and the Cochrane Library. Studies were considered eligible when DT incidence was reported after different types, approaches and timing of colectomy. Twenty studies including 6452 FAP patients were selected, all observational. No significant difference in DT incidence was observed after IRA versus IPAA (OR 0.99, 95% CI 0.69-1.42) and after open versus laparoscopic colectomy (OR 0.88, 95% CI 0.42-1.86). Conflicting DT incidences were seen after early versus late colectomy and when analysing open versus laparoscopic colectomy according to colectomy type. Three studies reported a (non-significantly) higher DT incidence after laparoscopic IPAA compared to laparoscopic IRA, with OR varying between 1.77 and 4.09. A significantly higher DT incidence was observed in patients with a history of abdominal surgery (OR 3.40, 95% CI 1.64-7.03, p = 0.001). Current literature does not allow to state firmly whether type, approach, or timing of colectomy affects DT risk in FAP patients. Fewer DT were observed after laparoscopic IRA compared to laparoscopic IPAA, suggesting laparoscopic IRA as the preferred choice if appropriate considering rectal polyp burden. PROSPERO REGISTRATION NUMBER: CRD42020161424.
Topics: Humans; Fibromatosis, Aggressive; Colectomy; Adenomatous Polyposis Coli; Laparoscopy; Incidence; Proctocolectomy, Restorative
PubMed: 35022961
DOI: 10.1007/s10689-022-00288-y -
Surgical Endoscopy Mar 2022This paper aimed to elucidate the etiologies of all primary ileostomy site malignancies published in the literature. (Review)
Review
BACKGROUND
This paper aimed to elucidate the etiologies of all primary ileostomy site malignancies published in the literature.
METHODS
A review of the literature was conducted following PRISMA guidelines by querying PubMed, Global Health, and Web of Science for articles published before November 2020. Search criteria contained broad terminology for ileostomy site neoplasms without language, date, or publication limitations. A full-text review of the abstracts confirmed primary malignant pathologies and was evaluated for study inclusion.
RESULTS
Literature search discovered 858 publications, with 76 meeting eligibility criteria. The final sample contained 91 patients, with equal males and females. The mean age of patients with ileostomy site malignancy was 62.0 ± 12.2, with an average ileostomy age of 29.4 ± 12.4. The most common indications for ileostomy creation were inflammatory bowel disease (IBD) (73.6%) and familial adenomatous polyposis (FAP) (20.9%). There was a total of eight ileostomy malignant pathologies reported, with adenocarcinoma being the most common (76.9%), followed by squamous cell carcinoma (SCC) (11.0%). Adenocarcinoma was diagnosed at a younger age than SCC (59.7 vs. 72.3) and developed over a shorter time (28.8 vs. 37.0). Patients with FAP almost exclusively developed adenocarcinoma (94.4%) at a younger stoma age (25.8 vs. 31.4) than those with IBD who developed seven diverse pathologies. With a median follow-up of 0.75 years, four patients developed disease recurrence and received oncologic resection of their cancer less often than the 55 negative patients (p = 0.04).
CONCLUSION
Ileostomy site malignancies are late-appearing complications that require curative surgery. Their presentation is associated with ileostomy duration and creation indication, such as FAP or IBD. We recommend screening at a stoma age ≥ 20 or patient age ≥ 50 for patients with FAP, while stoma age ≥ 25 or patient age ≥ 60 for IBD patients.
Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Female; Humans; Ileostomy; Male; Neoplasm Recurrence, Local; Surgical Stomas
PubMed: 34997348
DOI: 10.1007/s00464-021-08847-7 -
BMC Cancer Jan 2022Approximately 5% of colorectal cancer (CRC) cases are part of a well-defined inherited genetic syndrome and up to approximately 30% of these cases have a clinically...
BACKGROUND
Approximately 5% of colorectal cancer (CRC) cases are part of a well-defined inherited genetic syndrome and up to approximately 30% of these cases have a clinically defined familial basis. Psychosocial interventions in familial colorectal cancer address aspects mainly focused on affective, cognitive and behavioural outcomes. The present review aims to systematically map out the available psychosocial interventions for individuals with a family history of CRC and describe the current state of the research.
METHODS
An extensive electronic search was conducted to investigate the literature published until June 2020. Inclusion criteria consisted of quantitative studies published in English that explored the impact of psychosocial interventions for familial CRC, clearly defined the psychosocial intervention offered and included participants with a family history of CRC.
RESULTS
The analysis included 52 articles. Genetic counselling, educational interventions, psychological interventions and multimodal interventions were identified across the studies. In terms of diagnoses, Lynch Syndrome, Familial Adenomatous Polyposis, Familial Colorectal Cancer were the main conditions included in the studies. Affective, cognitive, behavioural aspects and quality of life emerged as the most frequently explored outcomes. The studies included individuals with both personal and familial history of CRC or family history alone.
CONCLUSIONS
Our rapid review provides an overview of the literature exploring the impact of psychosocial interventions for familial CRC. The psychosocial interventions identified had an overwhelmingly positive impact across all types of outcomes measured. Genetic counselling appeared to be most beneficial, and this is expected as it is purposively designed to address genetic conditions. Further quantitative analysis of primary empirical research is needed to determine the efficacy and effectiveness of psychosocial interventions as well as the mechanisms through which they exert their effect.
Topics: Adenomatous Polyposis Coli; Adult; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Female; Genetic Counseling; Humans; Male; Medical History Taking; Middle Aged; Psychosocial Intervention; Psychotherapy; Quality of Life
PubMed: 34980016
DOI: 10.1186/s12885-021-09086-8 -
International Forum of Allergy &... Jul 2022Bitter and sweet taste receptors (T2Rs and T1Rs), respectively, are involved in the innate immune response of the sinonasal cavity and associated with chronic...
BACKGROUND
Bitter and sweet taste receptors (T2Rs and T1Rs), respectively, are involved in the innate immune response of the sinonasal cavity and associated with chronic rhinosinusitis (CRS). Growing evidence suggests extraoral TRs as relevant biomarkers, but the current understanding is incomplete. This systematic review synthesizes current evidence of extraoral taste receptors in CRS.
METHODS
PubMed, Embase, Cochrane, Web of Science, and Scopus were reviewed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines and included studies of genotypic and phenotypic T2R/T1R status in CRS patients.
RESULTS
Twenty-two studies with 3845 patients were included. Seventeen studies evaluated genotype and 10 evaluated taste phenotypes. Four of 6 studies examining the haplotype distribution of the T2R, TAS2R38, demonstrated increased AVI/AVI haplotype ("nontaster") frequency in CRS. Meanwhile, 2 studies demonstrated decreased bitter sensitivity in CRS with nasal polyposis (CRSwNP), whereas 3 other studies reported decreased bitter sensitivity only in CRS without nasal polyposis (CRSsNP). Findings regarding sweet sensitivity were mixed. Three studies with cystic fibrosis patients (n = 1393) were included. Studies investigating the association between clinical outcomes and TAS2R38 alleles were limited, but the nonfunctional combination of AVI/AVI was associated with increased utilization of sinus surgery and, in CRSsNP patients, with poorer improvement of symptoms postoperatively.
CONCLUSION
Both genotypic and phenotypic assessments of T2Rs suggest a potential association with CRS, particularly CRSsNP. However, limited evidence and mixed conclusions cloud the role of T2Rs in CRS. Future investigations should aim to increase diverse populations, broaden institutional diversity, examine T1Rs, and utilize uniform assessments.
Topics: Chronic Disease; Humans; Nasal Polyps; Receptors, G-Protein-Coupled; Rhinitis; Sinusitis; Taste
PubMed: 34913601
DOI: 10.1002/alr.22938