Surveillance Compliance and Quality of Life Assessment Among Surgical Patients with Familial Adenomatous Polyposis Syndrome.

BACKGROUND: Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals in Saudi Arabia are unknown. We aimed to explore surveillance compliance in our population, as well as the disease impact on their quality of life (QoL). METHODS: All patients with FAP who underwent surgical resection at King Saud University Medical City between 2016 and 2022 were included. Demographic data, clinical features, family history, and compliance with surveillance were collected and analyzed. QoL questionnaires: Short-form health survey (SF-36) and European Organization for Research and Treatment (EORTC) were conducted by phone interview. RESULTS: A total of 14 patients were included with an average age of 25 years. Three patients (21.4%) were the first of their family members to develop FAP. Nine patients (64%) were untested for genetic mutation due to lack of referral to geneticists. The compliance rate toward both pre-operative colonoscopy and upper endoscopy were 78%. However, 38% and 27% compliance rates were observed toward initial and post-operative colonoscopy, respectively. The compliance rate was 14% toward thyroid ultrasound. QoL scores varied among patients, with a mean score above 60 across all SF-36 domains. CONCLUSION: An overall poor compliance was observed among our participants, particularly toward thyroid ultrasound. Increased health awareness and patient education are essential. In addition, the importance of surveillance and genetic counseling should be emphasized among physicians treating these patients.

Cost-effectiveness of preventive aspirin use and intensive downstaging polypectomy in patients with familial adenomatous polyposis: A microsimulation modeling study.

OBJECTIVE: Although there is increasing evidence to suggest the cost-effectiveness of aspirin use to prevent colorectal cancer (CRC) in the general population, no study has assessed cost-effectiveness in patients with familial adenomatous polyposis (FAP), who are at high risk of developing CRC. We examined the cost-effectiveness of preventive use of low-dose aspirin in FAP patients who had undergone polypectomy in comparison with current treatment practice. DESIGN: We developed a microsimulation model that simulates a hypothetical cohort of the Japanese population with FAP for 40 years. Three scenarios were created based on three intervention strategies for comparison with no intervention, namely intensive downstaging polypectomy (IDP) of colorectal polyps at least 5.0 mm in diameter, IDP combined with low-dose aspirin, and total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Cost-effective strategies were identified using a willingness-to-pay threshold of USD 50,000 per QALY gained. RESULTS: Compared with no intervention, all strategies resulted in extended QALYs (21.01-21.43 QALYs per individual) and showed considerably reduced colorectal cancer mortality (23.35-53.62 CRC deaths per 1000 individuals). Based on the willingness-to-pay threshold, IDP with low-dose aspirin was more cost-effective than the other strategies, with an incremental cost-effectiveness ratio of $57 compared with no preventive intervention. These findings were confirmed in both one-way sensitivity analyses and probabilistic sensitivity analyses. CONCLUSION: This study suggests that the strategy of low-dose aspirin with IDP may be cost-effective compared with IDP-only or IPAA under the national fee schedule of Japan.

Global burden and trends of the Entamoeba infection-associated diseases from 1990 to 2019: An observational trend study.

BACKGROUND: Entamoeba infection-associated diseases (EIADs) in humans are a worldwide public health problem, but there is a lack of a global picture of EIADs, which is vital to prevention and control. METHODS: We applied 2019 Global Burden of Disease (GBD) data collected from multiple sources at global, national and regional levels. The disability-adjusted life years (DALYs) with corresponding 95% uncertainty intervals (95% UIs) were extracted as the main measure of the burden of EIADs. The Joinpoint regression model was used to estimate the trends of age-standardised DALY rates by age, sex, geographical region, and sociodemographic index (SDI). Besides, a generalized linear model was conducted to analyze the influence of sociodemographic factors on the DALY rate of EIADs. RESULTS: In 2019, there were 2,539,799 (95% UI 850,865-6,186,972) DALY cases attributable to Entamoeba infection, and the global age-standardised DALY rate of EIADs was 36.77/100,000 (95% UI: 12.03-90.49). Although over the past 30 years, the age-standardised DALY rate of EIADs presented significantly declining trends [average annual percent change (AAPC) = -3.79%, 95% CI: -4.05% - -3.53%], it has remained a heavy burden among the age group of <5 years (257.43/100,000, 95% UI: 67.73-676.78) and the low SDI regions (100.47/100,000, 95% UI: 32.27-249.09). The age-standardized DALY rate in high-income North America and Australia had an increasing trend (AAPC = 0.38%, 95% CI: 0.47% - 0.28% and 0.38%, 95% CI: 0.46% - 0.29%, respectively). Furthermore, the DALY rates in high SDI regions showed statistically significant increasing trends among the age groups of 14-49, 50-69 years and 70+ years, with AAPCs of 1.01% (95% CI: 0.87% - 1.15%), 1.58% (95% CI: 1.43% - 1.73%), and 2.93% (95% CI: 2.58% - 3.29%), respectively. CONCLUSIONS: Over the past 30 years, the burden of EIADs has declined significantly. However, it has still caused a high burden in the low SDI regions and the age group of <5 years. At the same time, in adults and the elderly of the high SDI regions, the increasing trends of Entamoeba infection-associated burden should also be given more attention.

Serrated polyposis syndrome; epidemiology and management.

Serrated colorectal polyps, long considered innocent, are currently recognized as the precursors to one-third of all colorectal cancers (CRC). Serrated polyposis syndrome (SPS), characterized by accumulation of multiple and/or large serrated polyps, symbolizes the highest expression of serrated pathway of carcinogenesis, leading to a high risk of CRC when it is not detected or treated on time. Although previously considered uncommon, SPS is now acknowledged as the most prevalent colorectal polyposis. This syndrome has attracted increasing interest over the past decade and has become a hot topic in the field of gastrointestinal oncology. Besides a small proportion of cases caused by germline mutations in RNF43, no clear genetic cause has been identified. Both epigenetic and environmental factors, especially smoking, have been related to this syndrome, but the etiology of SPS remains uncertain and diagnosis is based on endoscopic criteria. Recent studies on SPS have focused on identifying the underlying risk-factors for CRC, defining the best endoscopic techniques for surveillance and establishing optimal preventive strategies aimed at reducing CRC-incidence without exposing patients to unnecessary procedures. The purpose of this chapter is to review, from a practical perspective, current knowledge and future directions in the diagnosis and management of serrated polyposis syndrome.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Paediatric polyposis syndromes: burden of disease and current concepts.

PURPOSE OF REVIEW: Polyposis syndromes are rare but significant entities that often present during childhood and adolescence. Polyposis syndromes should remain high on the differential diagnoses for any child presenting with rectal bleeding, protein-losing enteropathy or intussusception in the setting of multiple polyps in the gastrointestinal tract. There are three primary paediatric polyposis syndromes: Juvenile polyposis syndrome (JPS), Familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS). This review will cover recent guidelines for these conditions and advances in genetic testing. RECENT FINDINGS: The first set of paediatric guidelines were released in 2019 by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for FAP, JPS and PJS. Even with advances in genetic testing, a significant proportion of patients with polyposis syndromes have no identifiable genetic mutations. Recent research has shown that polyps behave differently in patients with and without disease-causing variants, emphasizing the role of genetic testing in the diagnosis and management of polyposis syndromes. SUMMARY: Polyposis syndromes in the paediatric population are growing due to increased recognition and advances in genetic testing. A timely diagnosis and surveillance of a paediatric polyposis syndrome are pivotal for the management of disease burden and early identification of cancers within the gastrointestinal tract and beyond. Paediatricians, paediatric gastroenterologists, paediatric oncologists and paediatric surgeons should be familiar with the presentation and comorbidities of polyposis syndromes in children and adolescents. Further research into genotype-phenotype correlations is needed to tailor the care for paediatric patients with polyposis syndromes.

Incidence and Management of Rectal Cuff and Anal Transitional Zone Neoplasia in Patients With Familial Adenomatous Polyposis.

BACKGROUND: Rectal cuff and anal transitional zone neoplasia is an increasing challenge in patients with familial adenomatous polyposis who have undergone restorative proctocolectomy. Its real incidence, range of severity, and treatment efficacy are poorly documented. OBJECTIVE: We sought to document the evolution of rectal cuff and anal transitional zone neoplasia and describe its management. DESIGN: This is a retrospective cohort study collecting prospectively recorded data. SETTINGS: This study involved a hereditary colorectal cancer group in a large academic medical center. PATIENTS: All patients undergoing primary restorative proctocolectomy at this institution were included. INTERVENTIONS: Surveillance pouchoscopy and treatment of rectal cuff/anal transitional zone neoplasia were performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the presence and the severity of rectal cuff/anal transitional zone neoplasia. Excision by cautery, snare, mucosectomy, or redo pouch was evaluated. RESULTS: A total of 165 patients were included: 52% were male (86/165) with a median age at restorative proctocolectomy of 31.0 years (SD 12.8). In 117 of 165, the proctocolectomy was their first operation and, in 48 of 165, it followed a colectomy. Of the patients, 83% (137/165) had stapled anastomosis; 17% had mucosectomy with handsewn anastomosis; and 14% (23/165) were treated with sulindac at some point during their surveillance. Median follow-up was 10.1 years (interquartile range, 4.5-17.2) and the median number of pouchoscopies per patient was 4 (interquartile range, 2-8). Seventy-eight of 165 (47.3%) developed rectal cuff/anal transitional zone adenomas, more in the stapled group (52.3%; 72/137) than in the handsewn group (21.4%; 6/28; p < 0.005). Median time to adenoma was 4.5 years (interquartile range, 2.4-8.9). Three patients developed cancer under surveillance, and, in 3 other patients, cancers developed when screenings lapsed. Five patients developed symptomatic anal stenosis secondary to repeated surgeries (median, 9 procedures; range, 2-10). LIMITATIONS: There was no quality-of-life measurement in patients who developed rectal cuff/anal transitional zone neoplasia. CONCLUSIONS: Rectal cuff/anal transitional zone adenomas are more common than previously reported. Mild polyposis can be controlled endoscopically, but repeated procedures in a higher stage are associated with risk of anal stenosis. Compliance with surveillance is essential to avoid cancer. See Video Abstract at http://links.lww.com/DCR/B594. INCIDENCIA Y TRATAMIENTO DE LA NEOPLASIA DEL REMANENTE RECTAL Y DE LA ZONA DE TRANSICIN ANAL EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: ANTECEDENTES:La neoplasia del remanente rectal y de la zona de transición anal presenta un desafío mayor en pacientes con poliposis adenomatosa familiar tratados con una proctocolectomía restaurativa. Su incidencia real, el espectro de la gravedad y la eficacia del tratamiento están mal documentados.OBJETIVO:Buscamos documentar la evolución de la neoplasia del remanente rectal y de la zona de transición anal y describir su tratamiento.DISEÑO:Estudio de cohorte retrospectivo que recabó datos registrados prospectivamente.AMBITO:Un grupo con cáncer colorrectal hereditario de un importante centro médico académico.PACIENTES:Todos los pacientes operados por primera vez de proctocolectomía restaurativa en nuestra institución.INTERVENCIONES:Endoscopía del pouch para vigilancia y tratamiento de la neoplasia del remanente rectal / zona de transición anal.PRINCIPALES VARIABLES ANALIZADAS:La presencia y la gravedad de la neoplasia del remanente rectal / zona de transición anal. Resección con cauterio, asa, mucosectomía o rehacer el pouch.RESULTADOS:Se incluyeron un total de 165 pacientes: 52% eran hombres (86/165) con una mediana de edad al momento de la proctocolectomía restaurativa de 31,0 años (DE 12,8). En 117/165 la proctocolectomía fue su primera cirugía y en 48/165 fue posterior a una colectomía. En 83% (137/165) tenía una anastomosis con engrapadora, 17% tenía mucosectomía y anastomosis con sutura manual (HS). El 14% de los pacientes (23/165) fueron tratados con sulindac en algún momento durante su vigilancia. La mediana de seguimiento fue de 10,1 años (IQR: 4,5, 17,2) y la mediana del número de endoscopías del pouch por paciente fue de 4. (IQR: 2, 8) 78/165 (47,3%) desarrollaron adenomas en la zona de transición anal /remanente rectal, mayor en el grupo con engrapadaora (52,3%; 72/137) comparado con el grupo con sutura manual (21,4%; 6/28) (p <0,005). La mediana del tiempo hasta el adenoma fue de 4,5 años (IQR: 2,4, 8,9). Tres pacientes que se encontraban en vigilancia desarrollaron cáncer y en 3, otros cánceres se desarrollaron transcurrida la vigilancia. 5 pacientes desarrollaron estenosis anal sintomática secundaria a múltiples cirugías (mediana de 9 procedimientos; rango 2-10).LIMITACIONES:Falta de medición de la calidad de vida en pacientes que desarrollaron neoplasia del remanente rectal / zona de transición anal.CONCLUSIONES:Los adenomas de la zona de transición anal / remanente rectal son más comunes de lo reportado anteriormente. La poliposis leve se puede tratar por endoscopía, pero procedimientos repetidos en estadíos mayores se asocian con el riesgo de estenosis anal. El apego a la vigilancia es fundamental para evitar el cáncer. Consulte Video Resumen en http://links.lww.com/DCR/B594. (Traducción-Dr. Lisbeth Alarcon-Bernes).

Assessment of circulating microRNA specific for patients with familial adenomatous polyposis.

Circulating microRNAs (miRNAs) are considered promising biomarkers for diagnosis, prognosis, and treatment efficacy of diseases. However, usefulness of circulating miRNAs as biomarkers for hereditary gastrointestinal diseases have not been confirmed yet. We explored circulating miRNAs specific for patients with familial adenomatous polyposis (FAP) as a representative hereditary gastrointestinal disease. Next-generation sequencing (NGS) indicated that plasma miR-143-3p, miR-183-5p, and miR-885-5p were candidate biomarkers for five FAP patients compared to three healthy donors due to moderate copy number and significant difference. MiR-16-5p was considered as an internal control due to minimum difference in expression across FAP patients and healthy donors. Validation studies by real-time PCR showed that mean ratios of maximum expression and minimum expression were 2.2 for miR-143-3p/miR-16-5p, 3.4 for miR-143-3p/miR-103a-3p, 5.1 for miR-183-5p/miR-16-5p, and 4.9 for miR-885-5p/miR-16-5p by using the samples collected at different time points of eight FAP patients. MiR-143-3p/16-5p was further assessed using specimens from 16 FAP patients and 7 healthy donors. MiR-143-3p was upregulated in FAP patients compared to healthy donors (P = 0.04), but not significantly influenced by clinicopathological features. However, miR-143-3p expression in colonic tumors was rare for upregulation, although there was a significant difference by existence of desmoid tumors. MiR-143-3p transfection significantly inhibited colorectal cancer cell proliferation compared to control microRNA transfection. Our data suggested regulation of miR-143-3p expression differed by samples (plasma or colonic tumors) in most FAP patients. Upregulation of plasma miR-143-3p expression may be helpful for diagnosis of FAP, although suppressive effect on tumorigenesis seemed insufficient in FAP patients.

The pouch behaving badly: management of morbidity after ileal pouch-anal anastomosis.

AIM: Ileal pouch-anal anastomosis (IPAA), or a 'pouch', allows restoration of intestinal continuity after proctocolectomy for ulcerative colitis or familial adenomatous polyposis. Most patients have a good long-term outcome after IPAA, but in a significant proportion the functional outcome and quality of life are unsatisfactory. We term this outcome 'the pouch behaving badly'. Managing this, especially one is when unfamiliar with the possible underlying pathologies, is a challenge for both patient and clinician. We aim to outline the clinical approach to the pouch behaving badly, highlighting key aspects of investigation and management. METHOD: This is a narrative review of the literature covering the investigation and management of postoperative complications and morbidity after IPAA. RESULTS: Management of the pouch behaving badly requires a careful clinical assessment. The patient may present with multiple symptoms and a clear picture of the symptomatology and past history should be constructed before thorough examination and specialist investigation. We divide the pathology that underlies this clinical scenario into surgical, inflammatory, mechanical, functional and dysplastic causes and outline the investigation and management of each one. CONCLUSION: The pouch behaving badly is a challenging problem for both patient and clinician. A detailed clinical assessment with careful specialist investigation is key to diagnosing the underlying pathology. We stress the importance of patient-centred care - the aim is to improve quality of life.

Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG).

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019.

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study.

BACKGROUND: Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES. PURPOSE: To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT). METHODS: The primary outcome was clinical sensitivity for the diagnosis of inherited CRCP; secondary outcomes included psychosocial outcomes, family communication, and healthcare resource utilization. Participants were surveyed 2 and 4 weeks after results return and at 3-month intervals up to 1 year. RESULTS: Evolving outcome measures and standard of care presented critical challenges. The majority of participants in the UC arm received multi-gene panels [94.73%]. Rates of genetic findings supporting the diagnosis of hereditary CRCP were 7.5% [7/93] vs. 5.4% [5/93] in the CES and UC arms, respectively (P = 0.28). Differences in privacy concerns after receiving CRCP results were identified (0.88 in UC vs 0.38 in CES, P = 0.05); however, healthcare resource utilization, family communication and psychosocial outcomes were similar between the two arms. More participants with positive results (17.7%) intended to change their life insurance 1  month after the first return visit compared to participants returned a variant of uncertain significance (9.1%) or negative result (4.8%) (P = 0.09). CONCLUSION: Our results suggest that CES provides similar clinical benefits to multi-gene panels in the diagnosis of hereditary CRCP.

Contribution to colonic polyposis of recently proposed predisposing genes and assessment of the prevalence of NTHL1- and MSH3-associated polyposes.

Technological advances have allowed the identification of new adenomatous and serrated polyposis genes, and of several candidate genes that require additional supporting evidence of causality. Through an exhaustive literature review and mutational screening of 177 unrelated polyposis patients, we assessed the involvement of MCM9, FOCAD, POLQ, and RNF43 in the predisposition to (nonserrated) colonic polyposis, as well as the prevalence of NTHL1 and MSH3 mutations among genetically unexplained polyposis patients. Our results, together with previously reported data and mutation frequency in controls, indicate that: MCM9 and POLQ mutations are not associated with polyposis; germline RNF43 mutations, with a prevalence of 1.5-2.5% among serrated polyposis patients, do not cause nonserrated polyposis; MSH3 biallelic mutations are highly infrequent among European polyposis patients, and the prevalence of NTHL1 biallelic mutations among unexplained polyposes is ~2%. Although nonsignificant, FOCAD predicted deleterious variants are overrepresented in polyposis patients compared to controls, warranting larger studies to provide definite evidence in favor or against their causal association with polyposis predisposition.

Assessment of Duodenal Adenomas and Strategies for Curative Therapy.

BACKGROUND: The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and histopathology. In this comprehensive review, we systematically describe the current knowledge concerning the diagnosis and management of duodenal adenomas (DAs) and discuss data considering all possible therapeutic approaches. SUMMARY: Among a variety of duodenal lesions, including neuroendocrine tumors and gastrointestinal stromal tumors, DAs present precancerous lesions of the duodenal papilla or non-ampullary region necessitating removal. DAs can occur sporadically (SDA) as rare lesions or relatively common in polyposis syndromes. The endoscopic resections of DA are associated with an increased degree of complexity due to distinctive anatomical properties of the duodenal wall, luminal diameter and the presence of ampulla with pancreatic and biliary drainage. The endoscopic techniques including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and argon plasma coagulation ablation are suggested to be less invasive than surgical treatment, associated with shorter hospital stay and lower cost. According to the current clinical practice, surgery has been accepted as standard therapeutic approach in familial adenomatous polyposis patients with severe polyposis or DA not amenable to endoscopic resection. Key Messages: The strategy for endoscopic resection of DAs depends on the lesion size, morphology, location, and histopathology findings. Small adenomas are most frequently diagnosed and removed by standard CSP techniques, while large laterally spreading lesions and ampullary adenoma are referred for EMR or endoscopic papillectomy respectively. Screening colonoscopy is indicated in patients with SDA. Additional studies for new endoscopic strategies and techniques for curative therapy of DAs are needed to refine future management decisions. Complete resection of DA is considered curative, but nevertheless, long-term endoscopic follow-up is still required to detect and treat any recurrent arising lesions.

A Decision Analysis for Rectal-Sparing Familial Adenomatous Polyposis: Total Colectomy With Ileorectal Anastomosis Versus Proctocolectomy With IPAA.

BACKGROUND: There are different approaches for the surgical management of rectal-sparing familial adenomatous polyposis with variable impacts on both quality of life and survival. OBJECTIVE: The aim of this study was to quantify the trade-offs between total proctocolectomy with IPAA versus total colectomy with ileorectal anastomosis using decision analysis. DESIGN: We created a disease simulation Markov model to simulate the clinical events after IPAA and ileorectal anastomosis for rectal-sparing familial adenomatous polyposis in a cohort of individuals at the age 30 years. We used available literature to obtain different transition probabilities and health-states utilities. The output parameters were quality-adjusted life-years and life-years. Deterministic and probabilistic sensitivity analyses were performed. SETTINGS: A decision analysis using a Markov model was conducted at a single center. PATIENTS: Patients with rectal-sparing familial adenomatous polyposis at age 30 years were included. Rectal-sparing familial adenomatous polyposis is defined as the presence of 0 to 20 polyps that can be removed endoscopically. MAIN OUTCOME MEASURES: Quality-adjusted life-years were measured. RESULTS: Our model showed that the mean quality-adjusted life-years for IPAA was 25.12 and for ileorectal anastomosis was 27.12 in base-case analysis. Mean life-years for IPAA were 28.81 and 28.28 for ileorectal anastomosis. A 1-way sensitivity analysis was performed for all of the parameters in the model. None of the deterministic sensitivity analyses changed the model results across the range of plausible values. Probabilistic analysis identified that, in 86.9% of scenarios, ileorectal anastomosis had improved quality-adjusted life-years compared with IPAA. LIMITATIONS: The study was limited by characteristics inherent to modeling studies. CONCLUSIONS: Ileorectal anastomosis was found to be preferable for patients with rectal-sparing familial adenomatous polyposis when quality of life is taken into consideration. This model was robust based on both deterministic and probabilistic sensitivity analyses. These data should be taken into consideration when counseling patients regarding a surgical approach in rectal-sparing familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/A715.

The cost-saving effect of centralized histological reviews with soft tissue and visceral sarcomas, GIST, and desmoid tumors: The experiences of the pathologists of the French Sarcoma Group.

OBJECTIVE: This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic impact of diagnostic discrepancies. METHODS: We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost. RESULTS: A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI [2.6-10.4]). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2. CONCLUSIONS: Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.

Dispelling misconceptions in the management of familial adenomatous polyposis.

Patients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.

Chemoprevention of colorectal neoplasia.

BACKGROUND: Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer. METHODS: An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990. RESULTS: The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present. CONCLUSIONS: Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups.