Surveillance Procedures Research Articles

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Cancer Risk in Patients with Gaucher Disease Using Real-World Data.

The association between GD and cancer has been uncertain due to ascertainment bias in previously published studies. We analyzed cancer incidence using the Maccabi Healthcare Service (MHS) electronic health records among 264 patients with GD compared to 3440 matched controls. We ascertained cancers diagnosed before and after the index date (i.e., the first documentation of GD in cases and the corresponding date for controls). Before the index date, cancers were diagnosed in 18 individuals, with 11 (4.2%) in the GD group and 7 (0.2%) in the control group. After the index date, cancers were diagnosed in 57 individuals, with 20 (7.9%) in the GD group and 37 (1.1%) in the control group, with a median follow-up of almost 13 years in both groups. The most common cancers diagnosed in GD were non-melanoma skin cancer (NMSC) and hematological malignancies, with a clustering of diagnoses around the time of GD diagnosis. The incidence of cancers (excluding MNSC) was 4.1 (95% CI 2.2-7.1) and 0.7 (95% CI 0.4-0.9) per 1000 patient-years in the GD and control groups, respectively, with an incidence rate ratio of 6.37 (95% CI 3-12.7). Patients with GD underwent more cancer screening tests than their counterparts in the control group. While our study revealed an increased occurrence of cancers in patients with GD, this finding might be partly attributed to the more rigorous surveillance procedures employed in this patient population.

Adherence to endoscopic surveillance guidelines for patients with inflammatory bowel disease: An Australian cohort study.

Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer as compared with the general population. Endoscopic surveillance to detect early dysplastic changes is advised by several published clinical guidelines, which provide recommendations as to the timing and performance of surveillance procedures. There is a paucity of data as to adherence with these guidelines in clinical practice. A longitudinal inception cohort study of all new patients diagnosed with inflammatory bowel disease across a service network of Australian hospitals between January 2005 and June 2014, with continuous follow-up in a gastroenterology clinic until December 31, 2022. Patients were included if they warranted surveillance according to the Australian guidelines. Adherence to guidelines and technical and quality measures were reported. A total of 136 patients were included, and a total of 263 surveillance procedures were performed. Ninety-five patients (70%) had their first surveillance colonoscopy within the correct time interval. Fifty patients (37%) were completely adherent to guidelines with respect to timing of all surveillance procedure. The overall dysplasia detection rate for surveillance procedures was 10%. Chromoendoscopy was only performed in 16% of procedures. Adherence to endoscopic surveillance guidelines with regard to timing of procedures and the utilization of chromoendoscopy is poor. Further clinician education, promotion of the surveillance guidelines and incorporation of chromoendoscopy training as part of the national colonoscopy training program may improve adherence to guidelines.

111 From abattoir-derived oocytes to in vitro-produced embryos: pathogen surveillance and washing procedures

111 From abattoir-derived oocytes to in vitro-produced embryos: pathogen surveillance and washing procedures

Artificial intelligence fails to improve colonoscopy quality: A single centre retrospective cohort study

BACKGROUND Limited data currently exists on the clinical utility of Artificial Intelligence Assisted Colonoscopy (AIAC) outside of clinical trials. AIM To evaluate the impact of AIAC on key markers of colonoscopy quality compared to conventional colonoscopy (CC). METHODS This single-centre retrospective observational cohort study included all patients undergoing colonoscopy at a secondary centre in Brisbane, Australia. CC outcomes between October 2021 and October 2022 were compared with AIAC outcomes after the introduction of the Olympus Endo-AID module from October 2022 to January 2023. Endoscopists who conducted over 50 procedures before and after AIAC introduction were included. Procedures for surveillance of inflammatory bowel disease were excluded. Patient demographics, proceduralist specialisation, indication for colonoscopy, and colonoscopy quality metrics were collected. Adenoma detection rate (ADR) and sessile serrated lesion detection rate (SSLDR) were calculated for both AIAC and CC. RESULTS The study included 746 AIAC procedures and 2162 CC procedures performed by seven endoscopists. Baseline patient demographics were similar, with median age of 60 years with a slight female predominance (52.1%). Procedure indications, bowel preparation quality, and caecal intubation rates were comparable between groups. AIAC had a slightly longer withdrawal time compared to CC, but the difference was not statistically significant. The introduction of AIAC did not significantly change ADR (52.1% for AIAC vs 52.6% for CC, P = 0.91) or SSLDR (17.4% for AIAC vs 18.1% for CC, P = 0.44). CONCLUSION The implementation of AIAC failed to improve key markers of colonoscopy quality, including ADR, SSLDR and withdrawal time. Further research is required to assess the utility and cost-efficiency of AIAC for high performing endoscopists.

Bayesian safety surveillance with adaptive bias correction.

Postmarket safety surveillance is an integral part of mass vaccination programs. Typically relying on sequential analysis of real-world health data as they accrue, safety surveillance is challenged by sequential multiple testing and by biases induced by residual confounding in observational data. The current standard approach based on the maximized sequential probability ratio test (MaxSPRT) fails to satisfactorily address these practical challenges and it remains a rigid framework that requires prespecification of the surveillance schedule. We develop an alternative Bayesian surveillance procedure that addresses both aforementioned challenges using a more flexible framework. To mitigate bias, we jointly analyze a large set of negative control outcomes that are adverse events with no known association with the vaccines in order to inform an empirical bias distribution, which we then incorporate into estimating the effect of vaccine exposure on the adverse event of interest through a Bayesian hierarchical model. To address multiple testing and improve on flexibility, at each analysis timepoint, we update a posterior probability in favor of the alternative hypothesis that vaccination induces higher risks of adverse events, and then use it for sequential detection of safety signals. Through an empirical evaluation using six US observational healthcare databases covering more than 360 million patients, we benchmark the proposed procedure against MaxSPRT on testing errors and estimation accuracy, under two epidemiological designs, the historical comparator and the self-controlled case series. We demonstrate that our procedure substantially reduces Type 1 error rates, maintains high statistical power and fast signal detection, and provides considerably more accurate estimation than MaxSPRT. Given the extensiveness of the empirical study which yields more than 7 million sets of results, we present all results in a public R ShinyApp. As an effort to promote open science, we provide full implementation of our method in the open-source R package EvidenceSynthesis.

Reining in Pegasus: The Oversight of the Spanish Intelligence Service in the Catalangate

The Pegasus spyware case, revealed in July 2021, also impacted Spanish politics when a report produced by Citizen Lab denounced that Catalan independentists had been surveilled using this software. The scandal — known as Catalangate — highlighted the need for a thorough audit of these surveillance capacities in the hands of the Spanish intelligence service. Using Catalangate as a case study, this article analyses whether Spanish mechanisms for controlling the surveillance capacities of the National Intelligence Centre (CNI) have followed the procedures established in Spanish legislation. Our conclusion is that the Spanish control system worked effectively. When the Parliamentary committee was unable to fulfill its duties, another actor within the democratic system, the Ombudsman, filled that gap. Secondly, the article analyses if Spanish control mechanism meets the more recent standards of case law from the European Court of Human Rights (ECHR), and the Court of Justice of the European Union (CJEU). This case law emphasises the importance of procedural guarantees for legitimising both bulk and targeted surveillance procedures, showing the need for potential improvements in Spanish regulations.

Distinct ways to perform a liver biopsy: The core technique setups and updated understanding of these modalities.

There is dramatically increased incidence of several liver diseases worldwide; thus, an unmet need to diagnose and stage these pathological entities heralds the wide application of liver biopsy (LB) techniques. The ways of LB are versatile, including percutaneous LB, transjugular LB, and more recently an approach of minimal invasiveness, that is, EUS-guided LB (EUS-LB). In this review article, we come to the conclusion that EUS-LB may serve as a feasible, reliable, and safe alternative to percutaneous LB and transjugular LB in terms of improved diagnostic yield, excellent sampling performance, and controlled adverse events among patients with focal, infiltrative, and parenchymal liver diseases. Furthermore, extensive efforts have been made to optimize and refine several technical pillars within EUS-LB modality such as the selection of needle size/type, priming manner of biopsy needle, and choice of pass/actuation technique, all of which aim at obtaining better specimen quantity and quality. Another advantageous aspect and unique property pertinent to EUS-guided modality indicate that multiple screening, surveillance, and intervention procedures can be combined into one single endoscopic session. Accordingly, some pilot studies have clarified the clinical usefulness by integrating EUS-LB with simultaneous measurement of portal pressure gradient or examination of liver stiffness. However, more studies, in particular, randomized controlled trials or real-world evidence, are practically warranted to elucidate the validity and safety of EUS-LB as a regular/routine part of managing liver diseases.

Implementasi Pemeliharaan Dan Penilikan Jalan Kabupaten Di Dinas Pekerjaan Umum Bina Marga Kabupaten Malang

The implementation of road maintenance and surveillance policies is useful for providing comfort to road users in accordance with the Regulation of the Minister of Public Works Number 13 of 2011 concerning Procedures for Road Maintenance and Surveillance. Efforts to implement the policy are to provide services in the form of repairs, prevention of road conditions so as not to cause problems. The purpose of this research is to find out the implementation of road maintenance and surveillance in accordance with the Regulation of the Minister of Public Works Number 13 of 2011 concerning Road Maintenance and Surveillance Procedures. The results show that the implementation of road maintenance policy in Malang District is hampered by the shortage of quantity and quality of human resources and financial resources. The lack of competent human resources and the lack of financial resources have an impact on the course of implementing road maintenance policies. From these obstacles, the results of road maintenance implementation are not as expected. On the other hand, the community considers that the government of the Malang Regency Bina Marga Public Works Office has provided and shown positive services and responses in the implementation of road maintenance in Malang Regency. Community support is also a motivation for the government in implementing road maintenance policies.

Correlation between Escherichia coli resistant gene isolated from stool samples of children under five years and that from consumed water

Diarrheagenic Escherichia coli (DEC) causes enteric infections and diarrhea, especially in young children. Kenya reports around 2.6 million cases and 7,000 deaths annually due to diarrhea. Antibiotic-resistant DEC strains are a significant public health concern, complicating treatment. The objective of this research was to correlate children's water consumption and antimicrobial-resistant DEC development. The study sampled 1124 children under five with diarrhea in Nakuru, Kenya, using a case-control design. Among 384 eligible children, 192 cases showed Amoxicillin-resistant DEC. Water samples from households were collected and analyzed for DEC presence. The samples were filtered, plated onto MacConkey agar, and subcultured onto Eosin Methylene Blue agar for further analysis. The DEC pathotypes were identified based on morphological and biochemical characteristics, and antibiotic resistance was assessed using the Kirby-Bauer disk diffusion method. The study revealed a strong correlation of 11.613 (95 % Confidence Interval [CI]: 6.495–20.765, p-value: 0.000) between microbial burden in vended water (water sold by vendors) used by different households consumption and antimicrobial resistance in DEC. Water sources showed a high prevalence of DEC, primarily Enteroaggregative, enteropathogenic, enterotoxigenic, and enteroinvasive E. coli. DEC isolates also exhibited varying antibiotic resistance, and genes like blaCTX-M, blaTEM, and blaSHV were identified using PCR. The Spearman correlation coefficient was one, showing that resistance genes in water and stool were perfectly correlated. The study emphasizes the significance of improving water quality, hygiene, and antibiotic-resistant bacteria control to prevent and manage DEC and infectious diseases in Kenya. To combat outbreaks, effective surveillance and rapid reaction procedures are essential. The findings help to shape public health policies and initiatives.

Towards improved short-term forecasting for Lake Victoria Basin: Part I – A radar-based convective mode analysis

Abstract East African countries benefit economically from the largest freshwater lake in Africa: Lake Victoria (LV). Around 30 million people live along its coastline and 5.4 million people subsist on its fishing industry. However, more than 1,000 fishermen die annually by high-wave conditions often produced by severe convective wind phenomena, which marks this lake one of the deadliest places in the world for hazardous weather impacts. The World Meteorological Organization launched the 3-year “HIGH impact Weather lAke sYstem” (HIGHWAY) project, with the main objective to reduce loss of lives and economic goods in the lake basin and improve the resilience of the local communities. The project conducted a field campaign in 2019 aiming to provide forecasters with high-resolution observations and to study the storm life cycle over the lake basin. The research discussed here used the S-band polarimetric Tanzania radar from the field campaign to investigate the diurnal cycle of the convective mode over the lake. We classified the lake storms occurring during the two wet seasons into six different convective modes and present their diurnal evolution, organization, and main radar-based attributes, thereby extending the knowledge of convection on the lake. The result is the creation of a “convection catalog for Lake Victoria,” using the operational forecast lake sectors, and defining the exact times for the different timeslots resulting from the HIGHWAY project for the marine forecast. This will inform methods to improve the marine operational forecasts for Lake Victoria, and to provide the basis for new Standard Operation Procedures (SOP) for severe weather surveillance and warning.

Oncological Surveillance After Radical Cystectomy: a Narrative Review of the Enhanced Recovery After Surgery Cystectomy Committee

Purpose: Follow-up after cystectomy aims to detect relapse, but there are discrepancies in recommendations among guidelines. Routine follow-up for asymptomatic recurrences in urothelial cancer is primarily based on nonvalidated risk factors from retrospective cohort studies in single institutions. This review provides an overview of follow-up investigations, schedules, and potential risk factors of recurrence. Materials and methods: We conducted a narrative literature search on PubMed and reviewed guidelines (European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, American Urology Association, and National Institute for Health and Care Excellence) and institutional protocols for cystectomy patients. Results: Our analysis included 29 studies with 23,218 patients. Most relapses occurred within 2 years, either locally or as distant recurrences in the chest, liver, bones, or brain. Factors increasing relapse risk included higher tumor stage, nodal involvement, histological subtypes, and lymphovascular invasion. Surveillance protocols varied in frequency and type of investigation. Limited recommendations were available for patients with ypT0, pT0, or non–muscle-invasive bladder cancer. Conclusions: Further research is needed to evaluate the impact of postcystectomy follow-up protocols on oncological outcomes and establish optimal surveillance procedures.

Molecular identification of ‘Candidatus Phytoplasma palmicola’ associated with coconut lethal yellowing in Equatorial Guinea

AbstractDuring the past two decades, a high mortality of coconut palms was observed in the coastal areas of Equatorial Guinea. Reportedly, the palm population has been reduced by 60%–70%, and coconut production has decreased accordingly. To identify the cause of the mortality, a survey was carried out in April 2021 in various localities of the coconut belt. Molecular analyses carried out on 16S rRNA and secA genes detected phytoplasma presence in the majority of the samples. Sequencing and BLAST search of the 16S rRNA gene sequences showed >99% identity of the detected phytoplasmas to ‘Candidatus Phytoplasma palmicola’. The RFLP analyses of 16S ribosomal gene using Tru1I and TaqI enzymes led to assign these phytoplasmas to subgroup 16SrXXII‐A. In all samples that tested positive, including one from a hybrid coconut palm and two from oil palm the same phytoplasma was identified. The phylogenetic analyses of 16S rRNA and secA genes confirmed respectively 99.98%–100% and 97.94%–100% identity to ‘Ca. P. palmicola’. RFLP analyses using MboII enzyme on the secA gene amplicon differentiated the phytoplasma found in Equatorial Guinea from those present in Ghana and Ivory Coast. The Equatorial Guinean phytoplasma strain resulted to be identical to the strains from Mozambique, confirming the presence of a geographic differentiation among phytoplasma strains in the coastal areas of Western and Central Africa. The identified phytoplasma is different from the ‘Ca. P. palmicola’ strains found in Ghana and Ivory Coast and represents the first identification a 16SrXXII‐A strain in Equatorial Guinea and in Central Africa. Strict monitoring and surveillance procedures for early detection of the pathogen are strongly recommended to reduce its impact and further spread in the country and permit the recovery of coconut plantations.

Unmet needs in Barret's esophagus diagnosis and treatment: a narrative review.

This narrative review discusses Barrett's esophagus management in the context of perceived deficiencies or controversies. Barrett's adenocarcinoma incidence has not clearly been impacted by Barrett's screening and surveillance. The following report was derived from articles using PubMed and Google searches. The search was concentrated on Barrett's esophagus screening and management guidelines. Comprehensive literature searches that highlight potential deficiencies or controversies regarding the current approach to Barrett's esophagus were employed. Esophageal adenocarcinoma incidence is rapidly increasing and this malignancy usually presents in an advanced and unresectable state. This is despite the significant expenditure of resources and time in endoscopic screening for and surveillance of Barrett's esophagus. Thus, more widespread screening for Barrett's esophagus may be considered. In addition, there are apparent inefficiencies and precision lack in the performance of endoscopic surveillance. This relates mainly to the lack of endoscopic cues for dysplasia. On the other hand, relatively low-risk subjects have frequent screening or surveillance procedures increasing cost. Lastly, endoscopic ablation for Barrett's with dysplasia has moderately good efficacy, especially for eradication of dysplasia, but mandates intensive post-therapy endoscopic surveillance. There is some concern for subsurface development of advanced Barrett's lesions. Fortunately, there is intense research in improving Barrett's esophagus diagnosis and treatment. Our narrative review will delineate deficiencies and potential measures to remedy them. In conclusion, screening for Barrett's esophagus and surveillance in Barrett's subjects have minimal established benefits, but proposed changes in screening practices and innovations in Barrett's esophagus endoscopic surveillance and dysplasia therapy have great promise.

O-115 Fertility preservation or egg donation for hereditary cancer syndromes?

Abstract Individuals with hereditary cancer syndromes are at risk of developing multiple tumours and, therefore, undergo life-long surveillance procedures and risk-reducing and/or therapeutic surgeries. Knowledge and testing for hereditary cancer susceptibility genes is rapidly spreading, often performed at the first cancer diagnosis. Different physical, psychosocial, ethical and economic considerations need to be taken into account when deciding on reproductive options in individuals with a hereditary cancer syndrome. The psychosocial impact of genetic predisposition to cancer may be particularly problematic and still represents an ongoing challenge for the professional taking care of these patients. In fact, worries about passing on a genetic risk for cancer to offspring are concerns expressed by the 65% of female young adult cancer survivors when specifically interviewed. At cancer diagnosis, fertility preservation procedures represent an effort to retain the opportunity to have genetically related children. Unfortunately, oocytes, embryo or ovarian cortex cryopreservation do not guarantee live birth. The success rates of these procedures are highly dependent on age, number of oocytes cryopreserved and may be influenced by other medical, lifestyle and (future) male factors. In addition, carriers of pathogenetic gene variants for cancer predisposition should also be thoroughly counselled about preimplantation genetic testing (PGT), a technique allowing the interruption of passing on the gene associated to cancer risk. However, this option inevitably lowers the efficacy of fertility preservation interventions in terms of future pregnancies. Egg donation is a spreading procedure with higher success rates than fertility preservation techniques. This approach allows individuals to avoid undergoing oocytes retrieval or ovarian tissue cryopreservation surgery, thus avoiding procedural risks (infection, haemorrhage, ovarian hyperstimulation syndrome) and postponement of oncological treatments. On the other side, offspring will not have a genetic link with recipient and the beneficial psychological role of fertility preservation would be missing. In fact, several recent studies have underlined the message of hope that is indirectly perceived by oncological patients when counselled for fertility preservation. Moreover, counselling on the possibility of egg donation is challenging at the time of cancer diagnosis. Making the right reproductive choice in carriers of hereditary cancer syndromes is a dilemma which can’t be solved generalizing. Even patients’ attitude could be different according to the time of counselling, whether is at cancer diagnosis or at the genetic predisposition diagnosis in healthy carriers. Egg donation should be considered in the available armamentarium. The complexity of the topic needs a personalized and multidisciplinary counselling.

Cancer surveillance for transgender and gender diverse patients with Lynch syndrome: a practice resource of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

Transgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals. There are no clinical guidelines specific for TGD individuals with LS, highlighting a need to improve the quality of care for this population. There is an urgent need for cancer surveillance recommendations for TGD patients. This commentary provides recommendations for cancer surveillance, risk-reducing strategies, and genetic counseling considerations for TGD patients with LS.

Comparing the resource implications of old and new colorectal adenoma surveillance guidelines in Australia.

The latest update to the Australian adenoma surveillance guideline in 2018 introduced a novel risk stratification system with updated surveillance recommendations. The resource implications of adopting this new system are unclear. To quanitfy the resource demands of adopting new over old adenoma surveillance guidelines. We studied data from 2443 patients undergoing colonoscopies, in which a clinically significant lesion was identified in their latest, or previous procedure(s) across five Australian hospitals. We excluded procedures with inflammatory bowel disease, new or prior history of colorectal cancer or resection, inadequate bowel preparation and incomplete procedures. Old and new Australian surveillance intervals were calculated according to the number, size and histological characteristics of lesions identified. We used these data to compare the rate of procedures according to each guideline. Based on the procedures for 766 patients, the new surveillance guidelines significantly increased the number of procedures allocated an interval of 1 year (relative risk (RR): 1.57, P = 0.009) and 10 years (RR: 3.83, P < 0.00001) and reduced those allocated to half a year (RR: 0.08, P = 0.00219), 3 years (RR: 0.51, P < 0.00001) and 5 years (RR: 0.59, P < 0.00001). Overall, this reduced the relative number of surveillance procedures by 21% over 10 years (25.92 vs 32.78 procedures/100 patient-years), which increased to 22% after excluding patients 75 or older at the time of surveillance (19.9 vs 25.65 procedures/100 patient-years). The adoption of the latest Australian adenoma surveillance guidelines can reduce demand for surveillance colonoscopy by more than a fifth (21-22%) over 10 years.

Neoplasia detection via colonoscopic surveillance among young patients with MSH6 and PMS2-associated Lynch syndrome.

10516 Background: Lynch syndrome (LS) is the most common colorectal cancer (CRC) predisposition syndrome. While patients (pts) with MLH1/ MSH2-associated LS are recommended to start colonoscopy between age 20-25, recent guidelines recommend delaying initiation in pts with MSH6/ PMS2-associated LS to age 30-35. However, data on findings from colonic surveillance in young MSH6/ PMS2-LS pts are limited. Methods: We performed a retrospective review of a multi-institutional cohort of pts with MSH6/ PMS2-associated LS who underwent any colonic surveillance prior to age 50, and assessed corresponding pathology results. Neoplastic lesions were defined as a CRC, adenomas, or non-hyperplastic serrated lesions. Clinicopathologic variables were reported with summary statistics and compared using non-parametric tests at the patient level and among pooled procedures. Results: We identified 285 pts [161(56%) MSH6; 124(44%) PMS2] with history of colonic surveillance prior to age 50. 190 (67%) pts were female, with similar sex distribution among the MSH6 and PMS2 groups. 107 (38%) pts had personal history (hx) of any cancer, 67 (42%) MSH6 and 40 (32%) PMS2, including 58 (20%) with CRC [35(22%) MSH6; 23 (19%) PMS2]. Median age at CRC diagnosis (dx) was 39 and did not differ between groups (41 MSH6 vs. 37 PMS2, p = 0.47) with 16 (5.6%) pts dx prior to age 35. 157 (57%) pts had a family hx of CRC, and there was no difference in the rate of CRC between pts with or without family hx of CRC [50%(n = 25) vs 60%(n = 31), p = 0.33]. Pts underwent a median of 2 colonic surveillance procedures (range 1-12) with 824 total procedures, 806 (98%) colonoscopies and 18 (2%) sigmoidoscopies, with 691 (85%) occurring at an academic/tertiary center. Among the 824 pooled procedures, there were 194 (24%) procedures with neoplastic lesions identified, including 19 (2.3%) with advanced adenomas or advanced serrated lesions and 34 (4.1%) with CRC. Among 247 procedures completed at age &lt; 35, 43 (18%) detected neoplastic lesions, including 4 (1.6%) with advanced adenomas or advanced serrated lesions and 9 (3.6%) with CRCs. Notably, in 123 procedures performed prior to LS diagnosis, 43 (35%) had a neoplastic finding with 28 (23%) showing CRC. These findings did not differ between the MSH6 and PMS2 groups. Conclusions: Among this large, multi-institutional cohort of pts with MSH6/ PMS2-associated LS with history of colonic surveillance performed prior to age 50, colonic neoplasia was found at similar rates in both MSH6 and PMS2-associated LS. 20% of overall pts had CRC, with 48% presenting prior to LS dx. In surveillance procedures performed &lt; age 35, the upper threshold of initiation of colonic surveillance as per NCCN, 18% found a neoplastic finding with 3.6% finding CRC, highlighting the need to optimize the age of colonic surveillance initiation in MSH6/ PMS2-associated LS.

FRI-323 - Exploration of a holistic management procedure for liver cancer surveillance to improve the early diagnosis of liver cancer in Chinese population

FRI-323 - Exploration of a holistic management procedure for liver cancer surveillance to improve the early diagnosis of liver cancer in Chinese population

Comprehensive analysis of patients with cancer with a positive CHEK2 test: Are we getting closer to a genotype/phenotype correlation?

10588 Background: The CHEK2 gene encodes a protein kinase that acts as a tumor suppressor with an important role in DNA damage repair. This gene is included in most hereditary breast, ovarian and prostate cancer panels, but the clinical actionability of CHEK2 pathogenic/likely pathogenic variants (PVs) may be challenging. Indeed, decisions concerning clinical surveillance and/or risk reducing procedures as well as screening for multiple associated cancer risks are not consensual. Our objective was to identify a potential genotype/phenotype association regarding CHEK2 PV identified in our population. Methods: Study group included all patients (pts) who tested positive for CHEK2 PVs between July 2000 and June 2022; control group included pts without PVs after multigene panel testing (wt) between January 2020 and June 2022. PVs were categorized as: truncating (includes nonsense, frameshift, splice site variants, gross deletions and duplications) and not truncating (missense and in-frame deletions). Clinical characteristics from both groups included gender, personal and family cancer history and tumor characteristics. Results: From 8604 pts tested, we identified 101 CHEK2 and 1506 wt pts. CHEK2 pts were mainly women (95; 92%) and Portuguese (94; 93.1%). All non-Portuguese pts had Eastern Europe ancestry. CHEK2 pts were either heterozygous (94;93%), homozygous (3; 3%) or had digenic inheritance (4; 6%: both a CHEK2 and a BRCA1/2 PV). Compared to wt pts, heterozygous CHEK2 pts were younger at 1st cancer diagnosis (44.5 yrs vs 47 yrs) and had more multiple primary cancers (OR: 1.8; p: 0.02). CHEK2 breast cancer was mostly but not exclusively estrogen receptor positive (69/78; 88,4%) and Her2 negative (54/69; 78%). Two BC cases had triple negative phenotype. The most frequent PVs detected were c.349A &gt; G (25 pts), c.1100del (24 pts) and c.319+2T &gt; A (20 pts). Considering heterozygous PVs, 57 were truncating and 37 non-truncating, with c. 1100del and c.349A &gt; G being the most frequent, in each group, respectively. For truncating versus non-truncating PVs there was no difference in phenotype regarding breast (OR: 0.69; p: 0.15), CRC (OR: 0.94; p: 0.91), gastric (OR: 0.76; p: 0.65), thyroid (OR: 1.3; p: 0,69) and kidney cancer (OR: 0.36; p: 0.27). Further stratification of PVs according to cancer type revealed a correlation of CRC with c.1100del (OR: 4.57; p: 0.0025) and c.349A &gt; G (OR: 5.49; p: 0.0003), while gastric, kidney and thyroid cancers correlated with c.349A &gt; G (OR: 5.8; p: 0.0069), c.1100del (OR: 26.86; p: 0.02) and c.319+2T &gt; A (OR: 3.31; p: 0.05) PVs, respectively. Conclusions: This analysis suggests a potential genotype-phenotype correlation regarding CHEK2 pathogenic variants, regardless of its truncating potential. The study of clinical outcomes will further contribute to determine how this information may influence the clinical and risk management of CHEK2 pts and their families.