The Spigelman Staging System and the Risk of Duodenal and Papillary Cancer in Familial Adenomatous Polyposis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Individuals with familial adenomatous polyposis (FAP) have an almost 20% lifetime risk of duodenal adenocarcinoma, currently the leading cause of death in FAP. The Spigelman staging system provides guidance on the surveillance intervals and timing of prophylactic surgery. Still, its accuracy in predicting duodenal and papillary cancer development has not been systematically evaluated. We investigated the sensitivity and cancer risk of the Spigelman stages. METHODS: We performed a systematic review on PubMed, MEDLINE, EMBASE, and Cochrane and used a random-effects model to pool effect sizes. RESULTS: After removing duplicate entries, we screened 1,170 records and included 27 studies for quantitative analysis. Once duodenal polyposis reaches Spigelman stage IV, the risk of duodenal and papillary cancers increased to 25% (95% confidence interval [CI] 12%-45%). However, the sensitivity of Spigelman stage IV for these cancers was low (51%, 95% CI 42%-60%), especially for papillary adenocarcinoma (39%, 95% CI 16%-68%). We investigated the reasons behind these low values and observed that duodenal cancer risk factors included polyps >10 mm, polyp count >20, and polyps with high-grade dysplasia. Risk factors associated with papillary cancer included a papilla with high-grade dysplasia or >10 mm. The evidence on other risk factors was inconclusive. DISCUSSION: The current Spigelman staging system had a low sensitivity for duodenal and papillary adenocarcinomas. Two Spigelman variables (duodenal villous histology and polyp count) and the lack of papilla-specific variables likely contributed to the low sensitivity values for duodenal and papillary cancers, respectively. While clinicians may be familiar with its current form, there is an urgent need to update it.

Comparing continent ileostomy (CI) conversion to repair/redo IPAA: favorable outcomes.

PURPOSE: This study aims to compare the outcomes of repair/redo ileal pouch-anal anastomosis (repair/redo-IPAA) with the conversion of IPAA to continent ileostomy (CI) in an effort to prevent the need for a permanent ileostomy (IS) following IPAA failure. METHODS: This research involved a retrospective analysis of surgical records, employing descriptive statistics and Kaplan-Meier survival analysis. RESULTS: Among 57 patients with an IPAA, up to three revisions were necessary due to complications or complete failure. Ultimately, repair/redo-IPAA preserved the IPAA in 14 patients (24.6%), conversion to CI salvaged the pouch in 21 patients (36.8%), and IS was unavoidable in 22 patients (38.6%). The cumulative probability of requiring conversion surgery was calculated to be 54.0% at 20 years, thereby reducing the cumulative risk of IS to 32.3%. The 20-year cumulative probability of pouch salvage by repair/redo IPAA was only 21.9%. However, this rate increased to 67.7% when conversion procedures were considered. Following repair/redo-IPAA, only 8.3% of patients reported evacuation frequencies of ≤ 4 during the day, and 16.7% were evacuation-free at night. In contrast, after conversion to CI, 98.0% of patients reported a maximum of four evacuations in a 24-h period. After undergoing repair/redo IPAA, between half and two-thirds of patients reported experiencing incontinence or soiling, while complete continence was achieved in all patients following conversion to CI. Notably, the majority of patients expressed overall satisfaction with their respective procedures. A positive correlation was identified between very high subjective satisfaction and positive objective surgical outcomes exclusively in patients who underwent conversion to CI. CONCLUSION: When complications or failure of IPAA occur, conversion to CI emerges as a highly viable alternative to repair/redo IPAA. This conclusion is supported by the observation that patient satisfaction appears to be closely tied to stable surgical outcomes. To reinforce these findings, further prospective studies are warranted.

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement.

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

[Management of the Peutz-Jeghers Syndrome]. / Management des Peutz-Jeghers-Syndroms.

The current evidence to guide management of Peutz-Jeghers Syndrome (PJS) is sparse. Here we summarise the European guidelines that were published in 2021 by the EHTG (European Hereditary Tumour Group), extended with new evidence on some aspects of clinical management that have been generated since then. EHTG with this revised guideline has updated and extended their own previous expert opinion guideline from 2010. For this purpose, all published literature was systematically screened and the level of evidence determined by using the GRADE methodology (Grading of Recommendations Assessment. Development and Evaluation). This was followed by a Delphi process and the consensus for a statement was achieved if the voting committee reached ≥ 80% approval.The only other more recently published guidelines encountered only addressed the clinical management of gastrointestinal and pancreatic manifestations of PJS. These recommendations were reviewed and adopted, since no further relevant literature was identified in the systematic literature search. However, additional questions were identified and formulated into recommendations after following the described process. It may be stated that 10 years after the predecessor guideline, new evidence has been sparse. As with all rare diseases, a call for more collaborative studies must here be made in order to improve patient management by addressing open clinical questions and generating collaborative evidence with increased case numbers, both nationally and internationally. With the limited published evidence, these European guidelines are the most current reference for management of PJS patients.

Is HLA type a possible cancer risk modifier in Lynch syndrome?

Lynch syndrome (LS) is the most common inherited cancer syndrome. It is inherited via a monoallelic germline variant in one of the DNA mismatch repair (MMR) genes. LS carriers have a broad 30% to 80% risk of developing various malignancies, and more precise, individual risk estimations would be of high clinical value, allowing tailored cancer prevention and surveillance. Due to MMR deficiency, LS cancers are characterized by the accumulation of frameshift mutations leading to highly immunogenic frameshift peptides (FSPs). Thus, immune surveillance is proposed to inhibit the outgrowth of MMR-deficient cell clones. Recent studies have shown that immunoediting during the evolution of MMR-deficient cancers leads to a counter-selection of highly immunogenic antigens. The immunogenicity of FSPs is dependent on the antigen presentation. One crucial factor determining antigen presentation is the HLA genotype. Hence, a LS carrier's HLA genotype plays an important role in the presentation of FSP antigens to the immune system, and may influence the likelihood of progression from precancerous lesions to cancer. To address the challenge of clarifying this possibility including diverse populations with different HLA types, we have established the INDICATE initiative (Individual cancer risk by HLA type, http://indicate-lynch.org/), an international network aiming at a systematic evaluation of the HLA genotype as a possible cancer risk modifier in LS. Here we summarize the current knowledge on the role of HLA type in cancer risk and outline future research directions to delineate possible association in the scenario of LS with genetically defined risk population and highly immunogenic tumors.

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up.

ABSTRACT: The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. PREVENTION RELEVANCE: Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.

Conversion of ileo-pouch anal anastomosis to continent ileostomy: strategic surgical considerations and outcome.

AIM: The aim was to evaluate surgical strategies for conversion of failed ileo-pouch anal anastomosis (IPAA) to continent ileostomy (CI), taking morbidity and overall outcome into account. The hypothesis was that complex conversions are equivalent to the primary construction of a CI at the time of proctocolectomy. METHOD: This was a retrospective analysis of IPAA conversions acknowledging the underlying disease (inflammatory bowel disease [IBD] and non-IBD) and extent of pouch reconstruction (PR): type 1 (without PR), type 2 (partial PR), and type 3 (complete PR). RESULTS: Twenty-six patients (IBD, n = 16; non-IBD, n = 10) were converted (type 1, n = 13; type 2, n = 7; and type 3, n = 6).12/26 patients (46.2%) presented postoperative complications directly related to the conversion with scarification of two pouches. In a mean follow-up time of 7.5 ± 6.6 years, 5/24 patients required revisional surgery. Of these, three required pouch excision. The cumulative probability of reoperation at the end of the second year increased to 21.7% and remained constant thereafter until the maximum follow-up time of 26 years. The total pouch loss rate was 19.2% (5/26), of which all occurred in the first 3 years. No statistically significant differences were found between the conversion types, complications or pouch survival. For all parameters, IBD patients performed slightly unfavourably. Due to the overall small number of respective patients, a differentiated investigation of IBD was not performed. CONCLUSION: Complex conversion procedures (types 1 and 2) deliver comparable long-term results to new constructions (type 3), thereby limiting the loss of small bowel. IBD compromises outcome versus non-IBD.

Salvage surgery for continent ileostomies (CI) after a first successful revision: more long-term blame on the reservoir than the nipple valve.

PURPOSE: The aim of the study was to investigate the underlying cause of long-term complications in patients requiring at least one revision surgery of a continent ileostomy (CI) and to analyze functional outcome. METHODS: Only patients with CI at least one revision were included in the retrospective data analysis. Four different classes of complications (Cl A-D) were defined: Cl A = Nipple valve (NV), Cl B = pouch, Cl C = outlet (stoma), and Cl D = afferent loop (AL). Associations between underlying disease and origin of complications were analyzed. Cumulative probabilities were calculated using Kaplan-Meier analysis. RESULTS: A total of 77 patients were identified with a follow-up of 30 years, requiring 133 surgeries for 148 complications (c.). Cl A 49 c. (33.1%), Cl B 50 c. (33.8%), Cl C 39 c. (26.4%), and Cl D 10 c. (6.8%). Cl A and C complications were not correlated to underlying disease, whereas Cl B and D complications were only found in ulcerative colitis (UC) and Crohn's disease (CD). The cumulative probability of a second revision showed a linear rise, reaching 62.5% after 20 years. Cl A and B complications both reached 42.1%. Eleven (14.3%) patients (10 Cl B) had pouch failure in a follow-up period of 11.5 ± 8.7 years (1-31 years), whereas 66 (85.7%) had successful revisional surgery. Overall CI survival was 78.8% at 44 years. CONCLUSION: CI survival is limited by inflammatory complications of the pouch based on the underlying disease and not by mechanical limitations of the NV. TRIAL REGISTRATION NUMBERS: None.

The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients.

BACKGROUND & AIMS: Owing to the high load of immunogenic frameshift neoantigens, tumors arising in individuals with Lynch syndrome (LS), the most common inherited colorectal cancer (CRC) syndrome, are characterized by a pronounced immune infiltration. However, the immune status of normal colorectal mucosa in LS is not well characterized. We assessed the immune infiltrate in tumor-distant normal colorectal mucosa from LS CRC patients, sporadic microsatellite-unstable (MSI) and microsatellite-stable (MSS) CRC patients, and cancer-free LS carriers. METHODS: CD3-positive, FOXP3-positive, and CD8-positive T cells were quantified in, respectively, 219, 233, and 201 formalin-fixed paraffin-embedded (FFPE) normal colonic mucosa tissue sections from CRC patients and cancer-free LS carriers and 26, 22, and 19 LS CRCs. CD3-positive T cells were also quantified in an independent cohort of 97 FFPE normal rectal mucosa tissue sections from LS carriers enrolled in the CAPP2 clinical trial. The expression of 770 immune-relevant genes was analyzed in a subset of samples with the use of the NanoString nCounter platform. RESULTS: LS normal mucosa specimens showed significantly elevated CD3-, FOXP3-, and CD8-positive T-cell densities compared with non-LS control specimens. Gene expression profiling and cluster analysis revealed distinct immune profiles in LS carrier mucosa with and without cancer manifestation. Long-term follow-up of LS carriers within the CAPP2 trial found a correlation between mucosal T-cell infiltrate and time to subsequent tumor occurrence. CONCLUSIONS: LS carriers show elevated mucosal T-cell infiltration even in the absence of cancer. The normal mucosa immune profile may be a temporary or permanent tumor risk modifier in LS carriers.

Variant profiling of colorectal adenomas from three patients of two families with MSH3-related adenomatous polyposis.

The spectrum of somatic genetic variation in colorectal adenomas caused by biallelic pathogenic germline variants in the MSH3 gene, was comprehensively analysed to characterise mutational signatures and identify potential driver genes and pathways of MSH3-related tumourigenesis. Three patients from two families with MSH3-associated polyposis were included. Whole exome sequencing of nine adenomas and matched normal tissue was performed. The amount of somatic variants in the MSH3-deficient adenomas and the pattern of single nucleotide variants (SNVs) was similar to sporadic adenomas, whereas the fraction of small insertions/deletions (indels) (21-42% of all small variants) was significantly higher. Interestingly, pathogenic somatic APC variants were found in all but one adenoma. The vast majority (12/13) of these were di-, tetra-, or penta-base pair (bp) deletions. The fraction of APC indels was significantly higher than that reported in patients with familial adenomatous polyposis (FAP) (p < 0.01) or in sporadic adenomas (p < 0.0001). In MSH3-deficient adenomas, the occurrence of APC indels in a repetitive sequence context was significantly higher than in FAP patients (p < 0.01). In addition, the MSH3-deficient adenomas harboured one to five (recurrent) somatic variants in 13 established or candidate driver genes for early colorectal carcinogenesis, including ACVR2A and ARID genes. Our data suggest that MSH3-related colorectal carcinogenesis seems to follow the classical APC-driven pathway. In line with the specific function of MSH3 in the mismatch repair (MMR) system, we identified a characteristic APC mutational pattern in MSH3-deficient adenomas, and confirmed further driver genes for colorectal tumourigenesis.

Continent ileostomy: short- and long-term outcomes of a forgotten procedure.

BACKGROUND: Continent ileostomy (CI) aims to provide control of gas and faecal evacuation; however, it is rarely performed. This paper reports on outcomes of CI in a large single-surgeon series. METHODS: All consecutive patients who underwent CI between 1986 and 2015 were reviewed. Patients were classified according to the CI procedure (single stage versus two stage) and according to the underlying disease conditions (inflammatory bowel disease (IBD) versus no IBD). Primary outcome measures were early mortality and complications requiring surgical revision within 30 days (group Ia), those requiring surgical revision within 1-12 months (group Ib), and long-term complications after more than 12 months (group II). Secondary outcome measures were pouch survival and quality of life (QoL) assessed using questionnaires for occupational, sports, sexual, and travel activities; patients undergoing CI after conversion from ileostomy. Analyses were performed using descriptive statistics and Kaplan-Meier curves for the long-term outcomes. RESULTS: Sixty-two consecutive patients (28 men, 34 women) who underwent CI were reviewed, including 48 with IBD, and 14 without inflammatory conditions. Mean(s.d.) follow-up was 14.4 (9.5) (range 1-30) years. Twenty-seven patients (44 per cent) developed group I complications, of which 25 were corrected successfully. Two patients dropped out of the analysis: one who died from sepsis and the other owing to pouch loss attributed to unsolvable nipple complications. Of the remaining 60 patients, 23 (38 per cent) developed between one and five group II complications. The cumulative probability of reoperation was 54. per cent at 25 years. Overall, pouch survival was achieved in 90 per cent. The two-stage approach led to significantly fewer complications in group Ia (single stage versus two stage: 8 of 25 versus 2 of 37; P = 0.005), whereas complication rates in group Ib (5 of 23 versus 14 of 37) and group II (9 of 23 versus 14 of 37) were similar. Four CIs failed because of IBD complications. CI pouch and function were preserved in all patients without IBD, whereas in the group with IBD 2 of 31 with ulcerative colitis and 2 of 17 with Crohn's colitis lost the CI owing to severe intractable inflammatory complications. In 16 patients who had conversion from ileostomy to CI, QoL improved significantly above precolectomy levels in all domains. CONCLUSIONS: CI remains an alternative to conventional ileostomy. Although affected by high reoperation rates, it has the benefit of a high rate of pouch survival.

The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline.

The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

Female Representation and Position Based on Facts and Members Views in the European Society of Coloproctology.

BACKGROUND: There is wide variation in gender distribution in colorectal surgery across different European countries. OBJECTIVE: This study aimed to evaluate female representation, implicit bias, and members' perception on female participation and representation at the European Society of Coloproctology 2017 annual scientific meeting. DESIGN: This was a retrospective mixed-methods cross-sectional observational study. SETTINGS: The study was conducted using data from the 2017 European Society of Coloproctology annual scientific meeting program and attendees. MAIN OUTCOME MEASURES: The primary outcome measure was the percentage of female speakers in the formal program and assessment for implicit bias. Secondary outcomes were the percentage of women attending the conference, the percentage of women serving on committees, and the results of the online survey. METHODS: Female representation was retrospectively quantified by role, session type, and topic. Implicit bias was measured classifying the introductions of speakers by moderators as formal (using a professional title) or informal (using name only), then further stratified by gender. An online survey was disseminated and analyzed to investigate the members' perception as a benchmark analysis. RESULTS: Disparities were found between sexes, with fewer women attending the conference (25%), serving as session chairs (8%), speakers (21%), and on committees (10%) compared with men. There were no differences across sexes regarding the formal or informal introduction. The survey among our members showed that significantly fewer women felt equally endorsed within the society compared with men (33% versus 63%; p < 0.001). LIMITATIONS: The retrospective design with data available to be analyzed was limited by the sessions recorded (27/49) and survey respondents (28%). CONCLUSIONS: Female representation within European Society of Coloproctology as chair, speaker, attendee, and committee member was much lower than male representation, both in absolute numbers and relative to membership. Greater awareness of this disparity and inclusiveness are aims of our society. The impact of these initiatives will be determined by reevaluating these metrics at the 2020 annual meeting. See Video Abstract at http://links.lww.com/DCR/B384. REPRESENTACIN Y POSICIN FEMENINA EN LA SOCIEDAD EUROPEA DE COLOPROCTOLOGA BASADA EN LOS HECHOS Y LAS OPINIONES DE SUS MIEMBROS: ANTECEDENTES:Existe una amplia variabilidad en la distribución de géneros en la cirugía colorrectal en los diferentes países de Europa.OBJETIVO:Evaluar la representación femenina, el sesgo implícito y la percepción de los miembros sobre la participación y representación femenina en el 12° Congreso científico anual de la Sociedad Europea de Coloproctología.DESIGN:Este fué un estudio observacional retrospectivo de métodos mixtos transversales.AJUSTES:Los análisis se realizaron utilizando los datos del programa cintífico de la reunión y los datos de los presentes en el Congreso de la ESCP en 2017.MEDIDAS PRINCIPALES DE RESULTADOS:La principal medida en el resultado fue el porcentaje de disertantes femeninas en el programa definitivo y la evaluación del sesgo implícito. Los resultados secundarios fueron el porcentaje de mujeres que asistieron a la conferencia, trabajaron en los comités y los resultados de la encuesta informática.METODOS:La representación femenina se cuantificó retrospectivamente según el rol, tipo de sesión y temas. Se midió el sesgo implícito clasificando las introducciones de los disertantes por parte de los moderadores de manera formal (usando un título profesional) o informal (usando solamente el nombre), y luego fueron estratificadas por género. Se difundió y analizó una encuesta informática para investigar la percepción de los miembros como análisis de referencia.RESULTADOS:Se encontraron disparidades de género, con menos mujeres presentes en la conferencia (25%), obrando como presidentes de sesión (8%), como disertantes (21%) y como miembros de comités (10%) comparadas con los hombres. No hubo diferencia entre sexos con respecto a la introducción formal o informal. La encuesta informática entre los miembros mostró significativamente que menos mujeres se sentían respaldadas igualitariamente dentro de la sociedad comparadas con los hombres (33% frente a 63%, p<0.001).LIMITACIONES:Diseño retrospectivo de datos limitados a las sesiones grabadas (27/49) y a los encuestados (28%) disponibles para el análisis.CONCLUSIONES:La representación femenina dentro de la Sociedad Europea de Coloproctología como presidente, disertante, asistente ó como miembro del comité fué mucho menor que la representación masculina, tanto en números absolutos como en relación con la membresía. Crear una mayor conciencia de esta disparidad de inclusión son prioridad en nuestra sociedad. El impacto de estas iniciativas se determinará re-evaluando estas variables en reuniones futuras. Consulte Video Resumen en http://links.lww.com/DCR/B384.

The "unnatural" history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance.

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.

Identification of Patients with Pancreatic Cancer by Electron Paramagnetic Resonance Spectroscopy of Fatty Acid Binding to Human Serum Albumin.

An effective biological marker for pancreatic adenocarcinoma (PAC) is not available so far. Here, we investigate how electron paramagnetic resonance (EPR) spectroscopy of spin-labeled fatty acid (FA) molecules binding to human serum albumin (HSA) in human serum is a suitable method for the identification of patients with PAC through detection of PAC-induced changes of FA binding to albumin. The functionality of HSA to bind FA is investigated in serum samples of 35 patients with PAC, 26 patients with benign pancreatic tumors (BPD), and 24 healthy individuals by continuous wave (CW) EPR spectroscopy by simply dissolving 16-DOXYL stearic acid as spin-labeled FA. It is found that FA binding to HSA in PAC is significantly modified when compared with healthy and BPD individuals. The PAC group could best be discriminated from the healthy group based on EPR characteristics at the loading ratio of 1:4 (HSA:FA), while patients with PAC and BPD are distinguishable at a loading ratio of 1:6. Using nanoscale distance measurements through double electron-electron resonance (DEER), it is found that the distribution of FAs in the HSA of one PAC patient is similar to that of FAs in healthy individuals. Combining all EPR spectroscopic data, this leads to a tentative molecular interpretation of only small changes in hydration at the protein's surface as origin of the detectable characteristics for PAC patients. Thus, EPR of FA/HSA binding is a simple and promising tool for clinical detection of patients with PAC and needs to be tested with larger ensembles of different patient groups.

Age-dependent performance of BRAF mutation testing in Lynch syndrome diagnostics.

BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age-specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS-associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population-based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF-mutant CRC and reported age were <50 years. Among 339 of 756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2 of 339 (0.6%) BRAF mutations were detected in patients <50 years. The inclusion of BRAF testing led to high risk of missing LS patients and increased costs at age <50 years. BRAF testing in patients <50 years carries a high risk of missing a hereditary cancer predisposition and is cost-inefficient. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without BRAF testing.