Bryson Katona

• MD, PhD
• Instructor at University of Pennsylvania

Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, poly...

Objectives Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome that may confer increased pancreatic cancer (PC) risk. This study assesses PC risk and the rate of pancreatic imaging abnormalities in LFS. Methods PC prevalence in LFS was calculated for individuals with a known TP53 variant from the IARC/NCI database. Pancreatic imaging st...

Purpose The age to initiate colonoscopy in MSH6 / PMS2 -associated Lynch Syndrome (LS) remains uncertain. Herein we characterize colonoscopy findings among young individuals with MSH6 / PMS2 -associated LS. Methods Retrospective review of a multi-institutional cohort of individuals with MSH6/PMS2 -LS undergoing colonoscopy prior to age 50 was perf...

Currently, those recommended to undergo pancreatic cancer (PC) surveillance include appropriately aged individuals at high risk of PC due to an identifiable genetic susceptibility or those without identifiable genetic susceptibility who nonetheless have a strong family history of PC. With increases in identification of individuals at high risk for...

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the late...

Background: The expected and optimal adenoma detection rate (ADR) is not well characterized in Lynch syndrome (LS). The aim of this study is to determine the ADR, the overall colorectal neoplasia detection rate (CNDR), proximal serrated detection rate (PSDR), and CRC detection rate (CRCDR) in an LS cohort. Methods: A retrospective study was perform...

Background The lifetime risk of pancreatic cancer in women with a germline mutation in BRCA1 and BRCA2 is not well established. In an international prospective cohort of female carriers of BRCA1 and BRCA2 mutations, the cumulative incidence of pancreatic cancer from age 40 until 80 years was estimated. Methods A total of 8295 women with a BRCA1 or...

Purpose Early-onset colorectal cancer (CRC) diagnosed under age 50 is increasing at alarming rates, with >75% of early-onset cases occurring in patients between 40 and 49 years old. Germline genetic risk evaluations are key to delivering high-quality care to these patients. Methods We conducted a single-arm pilot implementation study of a default...

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin’s functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin i...

BACKGROUND: A sensitive and specific blood biomarker test is needed to improve survival in PDAC through early detection. An initial discovery study analyzing more than 3000 proteins using both pre-selected immunoassays and the Olink proteomics platform identified 15 promising protein candidates, of which ten were successfully pre-verified for ELISA...

Importance Half of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs) are well known to significantl...

Individuals with hereditary pancreatic cancer risk include high risk individuals (HRIs) with germline genetic susceptibility to pancreatic cancer (PC) and/or a strong family history of PC. Previously, studies have shown that PC surveillance in HRIs can downstage PC diagnosis and extend survival leading to pancreatic surveillance being recommended f...

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer; however, the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of gastric cancer risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the patho...

Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. Me...

Lynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) and Helicobacter...

593 Background: Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷ Lu-DOTATATE has been used for neuroendocrine tumors (NETs) since its approval in the United States based on demonstrated progression-free survival benefit in grade 1-2 midgut NETs. The recommended dosing is 7.4 GBq (200 mCi) every 8 weeks for 4 doses in total. We examined the pos...

Simple Summary ¹⁷⁷Lu-DOTATATE is a radioactive drug that can treat advanced neuroendocrine tumors, a type of cancer. However, some patients do not benefit from ¹⁷⁷Lu-DOTATATE treatment and there is an unmet need to identify such patients before they receive the treatment. Currently, each patient needs to have a positive result on a scan, such as ⁶⁸...

Simple Summary This study explores the psychosocial impact of pancreatic cancer (PC) surveillance in individuals at high-risk (HRIs) of developing PC. The primary objective was to understand the attitudes and beliefs of HRIs undergoing PC surveillance and assess the immediate and sustained psychosocial effects. By investigating factors such as perc...

The initiation and progression of cancer are intricately linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorect...

429 Background: Young-onset colorectal cancer (yCRC) diagnosed under age 50 is increasing at alarming rates, with >75% of young-onset cases occurring in patients between 40-49 years old. Although national guidelines recommend germline genetic risk evaluations for all patients with yCRC, multiple studies have shown suboptimal rates of guideline-reco...

PURPOSE An effective blood-based test for pancreatic cancer (PC) screening has remained elusive. The IMMray PanCan-d is the first commercially available blood-based test specifically designed for early detection of PC; however, outcomes from its use in clinical practice have not been reported. METHODS We performed a blinded spike-in study of 100 i...

PURPOSE New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the America...

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority of cases initiated by inactivation of the APC tumour suppressor. This results in the constitutive activation of canonical WNT pathway transcriptional effector ß-catenin, along with induction of WNT feedback inhibitors, including the extracellular palm...

Background and aims: Menin is a nuclear scaffold protein that regulates gene transcription in an oftentimes tissue-specific manner. Our previous work showed that menin is over-expressed in colorectal cancer (CRC); however, the full spectrum of menin function in colonic neoplasia remains unclear. Herein, we aimed to uncover novel menin-regulated pa...

Pathogenic germline variants (PGVs) in the CDH1 gene are associated with diffuse gastric and lobular breast cancer syndrome (DGLBC) and can increase the lifetime risk for both diffuse gastric cancer and lobular breast cancer. Given the risk for diffuse gastric cancer among individuals with CDH1 PGVs is up to 30–40%, prophylactic total gastrectomy i...

Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on initial screening. Intervention and cancer detection rates on subsequent screenings are unknown...

Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March 2022 were col...

Unlabelled: Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March...

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...

Background International chemoprevention preferences and approaches in Lynch syndrome (LS) and APC- associated polyposis, including Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) have not been previously explored. Aim To describe current chemoprevention strategies for patients with LS or FAP/AFAP (referred to collectively as FAP) p...

Background The study purpose is to compare outcomes associated with completion of genetic testing between telemedicine and in-person gastrointestinal cancer risk assessment appointments during the COVID-19 pandemic. Methods Data was collected on patients with scheduled appointments between July 2020 and June 2021 in a gastrointestinal cancer risk...

Background: Inheritance patterns show familial clustering of gastrointestinal cancers, and multiple germline conditions have now been identified that predispose to colorectal, gastric, and pancreatic cancers. Methods: A narrative review based on recent relevant literature was conducted. Results: Lynch syndrome, formerly known as hereditary non...

687 Background: The international, multi-center Pancreatic Cancer Early Detection (PRECEDE) Consortium enrolls high-risk individuals (HRIs) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Enrollment began in 2020, and despite challenges related to the COVID-19 pandemic, the PRECEDE Consortium rapidly accrued a large cohort of HRIs....

689 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer typically discovered at incurable stages. The PRECEDE Consortium was established to accelerate early detection by using a large-scale, collaborative, innovative model, predicated on standardized collection of demographic, clinical, and imaging data from high-risk indi...

Carriers of a pathogenic germline variant (PV) in BRCA1 or BRCA2 are at increased risk for a number of malignancies, including breast, ovarian, pancreatic, and prostate cancer. In this review, we discuss emerging evidence that BRCA2 PV carriers, and likely also BRCA1 PV carriers, are also at increased risk for gastric cancer (GC), highlighting that...

Strong evidence demonstrates the protective benefit of frequent colonoscopy surveillance for colorectal cancer prevention in Lynch Syndrome (LS) and is endorsed by many guidelines. Until recently, the evidence supporting the utility of upper endoscopy [esophagogastroduodenoscopy (EGD)] for upper gastrointestinal (UGI) cancer surveillance was limite...

PURPOSE Whether germline multigene panel testing (MGPT) should be performed in all individuals with colorectal cancer (CRC) remains uncertain. Therefore, we aimed to determine the yield and potential clinical impact of MGPT across a large, diverse CRC cohort. METHODS This was a retrospective cohort study of adults with CRC who underwent MGPT of >...

Germline genetic testing for inherited cancer risk is increasingly being performed with multigene panel testing with MUTYH often included on colorectal cancer- and polyposis-focused panels, as well as on broader pan-cancer panels. With up to 1%-2% of the general population being monoallelic MUTYH carriers, pathogenic/likely pathogenic (P/LP) varian...

Purpose: With the recent guideline change for individuals at average risk for colorectal cancer (CRC) to initiate colonoscopy at the age of 45 years, there is a need to provide an updated counseling framework for individuals with variants in moderate-penetrance CRC susceptibility genes. Methods: Population age-specific incidence rates for CRC we...

The initiation and progression of cancer are inextricably linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorec...

Introduction: Germline variants in CDH1 are associated with elevated risks of diffuse gastric cancer and lobular breast cancer. It is uncertain if there is an increased risk of colorectal neoplasia. Methods: Retrospective analysis of colonoscopy outcomes in patients with germline CDH1 pathogenic/likely pathogenic variants. Results: Eighty-five...

Background and Aims Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper gastrointestinal (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility. Methods Databases were queried through...

Background Pathogenic variants (PV) of CTNNA1 are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germline CTNNA1 PV. Methods Data from published CTNNA1 families were updated and...

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of t...

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally, with the majority of cases initiated by inactivation of the APC tumor suppressor. This results in the constitutive transcriptional activation of the canonical WNT signal transduction pathway effector beta-Catenin, along with induction of WNT feedback inhibitors, including...

Background: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general po...

Background: Yearly whole-body MRI is recommended for cancer screening in patients with the rare high risk cancer predisposition syndrome, Li-Fraumeni syndrome (LFS). This is based on data from multiple studies demonstrating an approximately 7% cancer detection rate on baseline screening. However, the rate of actionable findings and malignancies on...

PURPOSE To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and...

10504 Background: Germline genetic testing for patients (pts) with colorectal cancer (CRC) is currently recommended for those diagnosed prior to age 50, as well as other select cases based on personal and/or family history criteria. Whether universal germline multi-gene panel testing (MGPT) should be performed in all pts with CRC remains uncertain...

e16239 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with lack of effective early detection strategies. There is an incomplete understanding of who is at risk for PDAC development and the contribution of heritability to that risk. Further, efforts at biomarker development for detection of early stage disease have be...

Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed¹. Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a st...

Background and study aims The majority of patients with 10 or more cumulative colorectal adenomas have uninformative genetic testing and meet criteria for colonic adenomatous polyposis of unknown etiology (CPUE). The yield of upper gastrointestinal screening in patients with CPUE after multi-gene panel testing is unknown and our objective was to ch...

Gastrointestinal cancers (GICs) and neuroendocrine tumors (NETs) are often refractory to therapy after metastasis. Adoptive cell therapy using chimeric antigen receptor (CAR) T cells, though remarkably efficacious for treating leukemia, is yet to be developed for solid tumors such as GICs and NETs. Here we isolated a llama-derived nanobody, VHH1, a...

Clinical guidelines recommend universal tumor screening (UTS) of colorectal and endometrial cancers for Lynch syndrome (LS). There are limited guidelines for how to integrate germline testing and somatic tumor testing after a mismatch repair deficient (dMMR) tumor is identified. We sought to characterize current practice patterns and barriers to pr...

Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer sur...

IntroductionThe IMMray PanCan-d test combines an 8-plex biomarker signature with CA19-9 in a proprietary algorithm to detect pancreatic ductal adenocarcinoma (PDAC) in serum samples. This study aimed to validate the clinical performance of the IMMray PanCan-d test and to better understand test performance in Lewis null (le/le) individuals who canno...

The goal of this review is to provide an overview of evaluating patients with adenomatous polyposis of the colon, including elements such as generating a differential diagnosis, referral considerations for genetic testing, genetic testing options, and expected outcomes from genetic testing in these individuals. In more recent years, adenomatous col...

Gastric cancer is one of the most significant causes of cancer-related morbidity and mortality worldwide. Recognized modifiable risk factors include Helicobacter pylori infection, geographic location, select dietary factors, tobacco use and alcohol consumption. In addition, multiple hereditary cancer predisposition syndromes are associated with sig...

Background: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers. While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines, there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS, including small...

Objective Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) encompass a diverse group of neoplasms that vary in their secretory products and in their location within the gastrointestinal tract. Their prevalence in the USA is increasing among all adult age groups. Aim To identify the possible derivation of GEP-NETs using genome-wide analyses...

Gestational diabetes mellitus(GDM) is a condition of glucose intolerance of glucose intolerance with onset or first recognition in pregnancy. Its incidence is increasing and GDM deleteriously affects both mother and fetus during and even after pregnancy. Previous studies in mice have shown that during pregnancy, β cell proliferation increases durin...

Patients newly diagnosed with metastatic pancreatic ductal adenocarcinoma generally have poor survival, with heterogeneous rates of progression. Biomarkers that could predict progression and/or survival would help inform patients and providers as they make care decisions. In a previous retrospective study, we discovered that circulating thrombospon...

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/Familia...

Carriers of a pathogenic/likely pathogenic (P/LP) BRCA1/BRCA2/ATM/PALB2 variant are at increased risk of pancreatic ductal adenocarcinoma (PDAC), yet current guidelines recommend surveillance only for those with a family history of PDAC. We aimed to investigate outcomes of endoscopic ultrasound (EUS)–based PDAC surveillance in BRCA1/BRCA2/ATM/PALB2...

Objectives: Data from the International Cancer of the Pancreas Screening Consortium studies have demonstrated that screening for pancreatic ductal adenocarcinoma can be effective and that surveillance improves survival in high-risk individuals. Endoscopic ultrasound (EUS) and cross-sectional imaging are both used, although there is some suggestion...

Purpose of review Cancer risk management for adenomatous oligopolyposis (10–99 colonic adenomas) depends upon whether the oligopolyposis results from a defined hereditary syndrome. Herein, we summarize genetic testing strategies for evaluation of oligopolyposis and outline colonoscopy and extra-colonic surveillance for individuals without a detecta...

PURPOSE Hepatocellular carcinoma (HCC) has well-defined environmental risk factors. In addition, epidemiologic studies have suggested hereditary risk factors. The goals of this study were to determine the rate of pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes in patients with HCC, possible enrichment of P/L...

Pancreatic beta cells undergo compensatory proliferation in the early phase of type 2 diabetes. While pathways such as FoxM1 are involved in regulating compensatory beta cell proliferation, given the lack of therapeutics effectively targeting beta cell proliferation, other targetable pathways need to be identified. Herein, we show that Pbk, a serin...

Background COVID-19 pandemic-related disruptions to pancreatic cancer EUS surveillance in high-risk individuals remain uncertain. Methods Analysis of enrolled participants in the CAPS5 Study, a prospective multicenter study of pancreatic cancer surveillance in high-risk individuals. Results Amongst 693 enrolled high-risk individuals under active...

Importance Peptide receptor radionuclide therapy (PRRT) is approved in the US for treatment of gastroenteropancreatic neuroendocrine tumors (NETs), but data on PRRT outcomes within US populations remain scarce. Objective To analyze the first 2 years of PRRT implementation at a US-based NET referral center. Design, Setting, and Participants This c...

Disruptions in cancer screening due to the COVID-19 pandemic may disproportionally affect patients with inherited cancer predisposition syndromes, including Lynch syndrome. Herein, we study the effect of the COVID-19 pandemic on endoscopic surveillance in Lynch syndrome through a prospective study of patients with Lynch syndrome at a tertiary refer...

Juvenile polyposis syndrome (JPS) is a clinically diagnosed hamartomatous polyposis syndrome that increases the risk of gastrointestinal cancer. Approximately 40-50% of JPS is caused by a germline disease-causing variant (DCV) in the SMAD4 or BMPR1A genes. The aim of this study is to characterize the phenotype of DCV-negative JPS and compare it to...

Introduction: To assess the upper gastrointestinal (UGI) cancer risk and surveillance outcomes in Li-Fraumeni syndrome (LFS). Methods: Analysis of the International Agency for Research on Cancer database and a single-center adult LFS cohort. Results: UGI cancer was present in 7.2% of families and 3.9% of individuals with a pathogenic/likely pa...