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INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. METHODS: All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses (International Classification of Disease, 10th Revision), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. RESULTS: The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP (P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25–2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17–1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19–2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20–1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09–2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10–3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24–2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26–2.70, P = 0.002). DISCUSSION: Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased, INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. METHODS: All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses ( International Classification of Disease, 10th Revision ), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. RESULTS: The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP ( P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25-2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17-1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19-2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20-1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09-2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10-3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24-2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26-2.70, P = 0.002). DISCUSSION: Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased likelihood of needing antidepressants an

Background and aims Pancreatic walled-off necrosis (WON) carries significant mortality and morbidity risks, often necessitating intensive care unit (ICU) admission. This retrospective study aimed to evaluate whether routine biochemical parameters at the time of the index endoscopic procedure could predict ICU admission and 1-year mortality following endoscopic treatment of WON. Materials and Methods We retrospectively identified 201 consecutive patients who underwent endoscopic drainage for WON between January 1, 2010, and December 31, 2020. Associations between routine biochemical blood tests and outcomes were assessed using logistic regression models. Results Within 1 year of the index endoscopy, 31 patients (15.4%) died, and 40 (19.9%) were admitted to the ICU due to sepsis. Preoperative electrolyte disturbances were more prevalent among ICU-admitted patients and nonsurvivors. Hyperkalemia, hypoalbuminemia, and elevated urea were significant predictors of 1-year mortality, while hypernatremia, elevated serum creatinine, and hypoalbuminemia predicted ICU admission. Predictive models exhibited good discriminative ability, with an AUC of 0.84 (95% CI,0,75–0.93) for 1-year mortality and 0.86 (95%CI, 0.79–0.92) for ICU admission. Conclusions Preoperative imbalances in routine blood tests effectively predict adverse outcomes in endoscopically treated WON patients., Background and aims Pancreatic walled-off necrosis (WON) carries significant mortality and morbidity risks, often necessitating intensive care unit (ICU) admission. This retrospective study aimed to evaluate whether routine biochemical parameters at the time of the index endoscopic procedure could predict ICU admission and 1-year mortality following endoscopic treatment of WON. Materials and Methods We retrospectively identified 201 consecutive patients who underwent endoscopic drainage for WON between January 1, 2010, and December 31, 2020. Associations between routine biochemical blood tests and outcomes were assessed using logistic regression models. Results Within 1 year of the index endoscopy, 31 patients (15.4%) died, and 40 (19.9%) were admitted to the ICU due to sepsis. Preoperative electrolyte disturbances were more prevalent among ICU-Admitted patients and nonsurvivors. Hyperkalemia, hypoalbuminemia, and elevated urea were significant predictors of 1-year mortality, while hypernatremia, elevated serum creatinine, and hypoalbuminemia predicted ICU admission. Predictive models exhibited good discriminative ability, with an AUC of 0.84 (95% CI,0,75-0.93) for 1-year mortality and 0.86 (95%CI, 0.79-0.92) for ICU admission. Conclusions Preoperative imbalances in routine blood tests effectively predict adverse outcomes in endoscopically treated WON patients.

Acute pancreatitis is associated with numerous complications. Pancreatic-portal vein fistula (PPVF) is an exceptionally rare and diagnostically challenging example [1] [2]. A 63-year-old man was admitted due to abdominal pain, weight loss, newly diagnosed diabetes, and elevated liver enzymes. Contrast-enhanced computed tomography revealed acute pancreatitis with fluid exudation and a necrotic collection in the head of the pancreas, accompanied by attenuation of fluid in the portal vein. Subsequent magnetic resonance cholangiopancreatography raised suspicion of PPVF. Endoscopic retrograde cholangiopancreatography (ERCP) identified a stenosis in the pancreatic duct (PD) at the head of the pancreas, associated with an upstream fluid collection and a fistula into the portal vein. The PD was not visible as the contrast injection passed into the portal vein ([Video 1]). The therapeutic intervention included pancreatic sphincterotomy with dilation of the PD stenosis with a 6-mm balloon catheter. Two 7 cm × 7 Fr double-pigtail stents were positioned within the fluid collection. The patient developed septicemia, which was treated with antibiotics. The patient was discharged after 45 days of hospitalization.

In the Danish Polyposis Register, patients with over 100 cumulative colorectal adenomas of unknown genetic etiology, named in this study colorectal polyposis (CP), is registered and treated as familial adenomatous polyposis (FAP). In this study, we performed genetic analyses, including whole genome sequencing (WGS), of all Danish patients registered with CP and estimated the detection rate of pathogenic variants (PV). We identified 231 families in the Polyposis Register, 31 of which had CP. A polyposis-associated gene panel was performed and, if negative, patients were offered WGS and screening for mosaicism in blood and/or adenomas. Next-generation sequencing (NGS) was carried out for 27 of the families (four declined). PVs were detected in 11 families, and WGS revealed three additional structural variants in APC. Mosaicism of a PV in APC was detected in two families. As the variant detection rate of eligible families was 60%, 93% of families in the register now have a known genetic etiology.

Chronic pancreatitis (CP) is the end-stage of continuous inflammation and fibrosis in the pancreas evolving from acute- to recurrent acute-, early, and, finally, end-stage CP. Currently, prevention is the only way to reduce disease burden. In this setting, early detection is of great importance. Due to the anatomy and risks associated with direct sampling from pancreatic tissue, most of our information on the human pancreas arises from circulating biomarkers thought to be involved in pancreatic pathophysiology or injury. The present review provides the status of circulating biomarkers involved in the development of and progression to CP.

Background and Aims EUS-guided drainage and, if required, endoscopic necrosectomy (EN) has become the criterion standard for the treatment of pancreatic walled-off necrosis (WON). A dedicated powered endoscopic debridement system, the EndoRotor (Interscope Inc, Northbridge, Mass, USA), has been introduced as an alternative to snare necrosectomy. This study evaluates the novel EndoRotor catheter, NecroMax 6.0 (Interscope Inc, Whitinsville, Mass, USA), for EN in patients with WON. Methods This single-center retrospective case series included consecutive patients with WON treated with the NecroMax 6.0 catheter. Safety, ability to perform EN, and clinical resolution were evaluated. Results Twenty patients underwent 30 EN procedures with the NecroMax 6.0 catheter. One suspected device-related adverse event was observed (3.3%). In 1 procedure, EN could not be performed because of excessive bending of the endoscope. Eighteen patients (90.0%) achieved clinical resolution. Conclusions EN with the NecroMax 6.0 catheter was technically feasible in 96.7% of patients with a low rate of adverse events., Background and Aims: EUS-guided drainage and, if required, endoscopic necrosectomy (EN) has become the criterion standard for the treatment of pancreatic walled-off necrosis (WON). A dedicated powered endoscopic debridement system, the EndoRotor (Interscope Inc, Northbridge, Mass, USA), has been introduced as an alternative to snare necrosectomy. This study evaluates the novel EndoRotor catheter, NecroMax 6.0 (Interscope Inc, Whitinsville, Mass, USA), for EN in patients with WON. Methods: This single-center retrospective case series included consecutive patients with WON treated with the NecroMax 6.0 catheter. Safety, ability to perform EN, and clinical resolution were evaluated. Results: Twenty patients underwent 30 EN procedures with the NecroMax 6.0 catheter. One suspected device-related adverse event was observed (3.3%). In 1 procedure, EN could not be performed because of excessive bending of the endoscope. Eighteen patients (90.0%) achieved clinical resolution. Conclusions: EN with the NecroMax 6.0 catheter was technically feasible in 96.7% of patients with a low rate of adverse events.

Introduction: The risk of cancer in patients with solitary colorectal juvenile polyps (JPs) is poorly investigated and several studies have reported polyps with dysplastic and adenomatous alterations. We aimed to investigate the long-term risk of cancer and mortality in these patients by merging data from national registers and comparing them to a matched control cohort. Materials and Methods: Patients with a solitary JP were identified in The Danish National Pathology Register and Data Bank (DNPR). The included patients were matched on sex, age, and place of birth with 50 controls. The groups were then analyzed for risk of cancer using the Danish Cancer Registry and mortality using the Danish Cause of Death Registry. Results: We identified 1781 patients with solitary JPs and matched them with 83,713 controls. The mean follow-up time was 7.65 years for cases and 7.36 years for controls. The risk of cancer, including colorectal cancer, did not differ for the two groups and when adjusting for sex and year of birth, the hazard ratio (HR) was 1.15 (confidence interval [CI] 95% 0.94–1.41, p = 0.162). There was no increased risk of death (HR: 1.07, CI 95% 0.88–1.30, p = 0.486). The risk did not differ for different age groups or sex. Conclusion: There is no increased risk of cancer or mortality for patients with solitary colorectal JPs. Thus, endoscopic follow-up may be safely omitted in these patients.

Background and study aims Transgastric endoscopic ultrasound (EUS)-guided drainage and, if needed, necrosectomy is the preferred treatment in patients with pancreatic walled-off necrosis. EUS-guided transcolonic or transrectal drainage and necrosectomy may serve as a minimally invasive alternative in cases in which transgastric or percutaneous drainage is either impossible or fails to secure sufficient drainage. In this paper, we retrospectively evaluated the feasibility, safety, and efficacy of the treatment. We included nine patients and found a technical success rate of 100%, clinical success in 89%, and one adverse event (11%). Transrectal/transcolonic endoscopic necrosectomy was needed in seven patients (78%).

Juvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected in SMAD4 or BMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant in BMPR1A or SMAD4. In patients where no variant had been detected, we performed genetic analysis, including whole genome sequencing. We collected clinical information on all patients to investigate the phenotypic spectrum. Sixty-six patients (mean age 40 years) were included of whom the pathogenic variant was unknown in seven patients. We detected a pathogenic variant in SMAD4 or PTEN in additional three patients and thus ≈ 95% of patients had a pathogenic germline variant. Endoscopic information was available in fifty-two patients (79%) and of these 31 (60%) fulfilled the clinical criteria of JPS. In 41 patients (79%), other types of polyps than juvenile had been removed. Our results suggest that almost all patients with a clinical diagnosis of JPS has a pathogenic variant in mainly BMPR1A, SMAD4, and more rarely PTEN. However, not all patients with a pathogenic variant fulfil the clinical criteria of JPS. We also demonstrated a wide clinical spectrum, and that the histopathology of removed polyps varied.

In this editorial we present an overview and insights of the management of hereditary polyposis syndromes. The primary focus was on familial adenomatous polyposis, juvenile polyposis syndrome and Peutz-Jegher syndrome. Genetic testing has become increasingly available and is easier than ever to integrate into clinical practice. Furthermore, several genes have been added to the expanding list of genes associated with hereditary polyposis syndromes, allowing for precise diagnostics and tailored follow-up. Endoscopic evaluation of patients with hereditary polyposis syndromes is paramount in the surveillance strategies. Current endoscopic procedures include both diagnostic procedures and surveillance as well as therapeutic interventions. Recommendations for endoscopic procedures in the upper and lower gastrointestinal canal were described. Surgery is still a key component in the management of patients with hereditary polyposis syndromes. The increased cancer risk in these patients often render prophylactic procedures or intended curative procedures in the case of cancer development. Surgical interventions in the upper and lower gastrointestinal canal were described with relevant considerations. Development of chemopreventive medications is ongoing. Few drugs have been investigated, including nonsteroidal anti-inflammatory drugs. It has been demonstrated that cyclooxygenase-2 inhibitors may lower the number of polyps. Other medications are currently under investigation, but none have, to date, consistently been able to prevent development of disease.

Background: Guidelines from the European Hereditary Tumor Group as well as The Danish National Guidelines for Peutz–Jeghers Syndrome (PJS) state that both prenatal diagnosis and preimplantation genetic testing for monogenic disorders (PGT-M) should be offered to patients with PJS. However, only a few cases resulting in viable pregnancies have been published. Objective: We present two cases of PJS patients going through PGT-M for PJS. We highlight the awareness of this possibility and discuss the technical and ethical challenges of performing PGT-M for PJS. Methods and results: Case 1: A 36-year-old male with PJS and his partner were referred for genetic counseling. The patient carried a pathogenic de novo variant in STK11. After a terminated pregnancy of a fetus carrying the same pathogenic variant, microsatellite polymorphic marker analysis was established, and the patient was offered PGT-M. The female partner of the patient gave birth to a healthy boy after five years of fertility treatment. Case 2: A 35-year-old female with PJS and her partner were referred for genetic counseling. She carried an inherited pathogenic STK11 variant. The couple was offered PGT-M. Genetic testing of the embryos was performed using microsatellite polymorphic markers. After two rounds of oocyte extraction a blastocyst predicted not to be affected by PJS was identified. The blastocyst was transferred; however, this did not result in a viable pregnancy. Conclusions: PGT-M can be offered to patients with PJS. The process may be long and filled with ethical dilemmas requiring patients to be motivated and persistent.

Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed., Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.

Objective: In treating pancreatic walled-off necrosis (WON), lumen-apposing metal stents (LAMS) have not proven superior to the traditional double pigtail technique (DPT). Among patients with large WON (>15 cm) and their associated substantial risk of treatment failure, the increased drainage capacity of a novel 20-mm LAMS might improve clinical outcomes. Hence, we conducted a study comparing the DPT and 20-mm LAMS in patients with large WON. Design: A single-centre, open-label, randomised, controlled superiority trial using an endoscopic step-up approach in patients with WON exceeding 15 cm in size. The primary endpoint was the number of necrosectomies needed to achieve clinical success (clinical and CT resolution), while the secondary endpoints included technical success, adverse events, length of stay and mortality. Results: Twenty-two patients were included in the DPT group and 20 in the LAMS group, with no significant differences in patient characteristics. The median size of WON was 24.1 cm (P25-P75: 19.6-31.1). The technical success rates were 100% for DPT and 95% for LAMS (p=0.48), while clinical success rates were 95.5% and 94.7%, respectively (p=1.0). The mean number of necrosectomies was 2.2 for DPT and 3.2 for LAMS (p=0.42). Five patients (12%) developed procedure-related serious adverse events (DPT=4, LAMS=1, p=0.35). The median length of stay was 43 (P25-P75: 40-67) and 58 days (P25-P75: 40-86) in the DPT and LAMS groups (p=0.71), respectively, with an overall mortality of 4.8%. Conclusions: For treating large WON, LAMS are not superior to DPT. The techniques are associated with comparable needs for necrosectomy and hospital stay, and no gross difference in adverse events. Trial registration number: NCT04057846.

Background and Objectives Several types of needles are available for EUS–guided tissue sampling of pancreatic lesions. Whereas fine-needle aspiration (FNA) needles typically provide cytological samples, fine-needle biopsy (FNB) needles are designed to obtain microcores with preserved tissue architecture. The aim of this study was to compare tissue amount and diagnostic yield between a modified Franseen-type FNB needle (TopGain; Medi-Globe GmbH, Grassau, Germany) and a standard FNA needle. Methods We performed a prospective, multicenter randomized controlled study between June 2020 and September 2021, including patients with a solid pancreatic lesion referred for EUS-guided tissue sampling at 3 centers in Denmark. The patients were randomized 1:1 to either FNA needle or the novel FNB needle. Primary outcomes included the number of obtained tissue microcores and total and diagnostic tissue area. Results Sixty-four patients were included. The median number of tissue microcores procured per pass was significantly higher in the FNB group compared with FNA (3 vs. 2, P < 0.001). Similarly, the mean total tissue area (2.74 vs. 0.44 mm2, P < 0.001) and mean diagnostic tissue area (1.74 vs. 0.28 mm2, P < 0.001) were more than 6-fold larger in the FNB samples compared with FNA. The median number of passes needed for a diagnostic sample was 1 for the FNB needle and 2 for FNA needle (P = 0.12). The novel FNB needle provided a higher percentage of samples of excellent quality (P = 0.002). Conclusions The novel Franseen-type FNB needle seems to be significantly superior to a conventional FNA needle. The results of this study underline excellent performance of crown-cut needles., BACKGROUND AND OBJECTIVES: Several types of needles are available for EUS-guided tissue sampling of pancreatic lesions. Whereas fine-needle aspiration (FNA) needles typically provide cytological samples, fine-needle biopsy (FNB) needles are designed to obtain microcores with preserved tissue architecture. The aim of this study was to compare tissue amount and diagnostic yield between a modified Franseen-type FNB needle (TopGain; Medi-Globe GmbH, Grassau, Germany) and a standard FNA needle.METHODS: We performed a prospective, multicenter randomized controlled study between June 2020 and September 2021, including patients with a solid pancreatic lesion referred for EUS-guided tissue sampling at 3 centers in Denmark. The patients were randomized 1:1 to either FNA needle or the novel FNB needle. Primary outcomes included the number of obtained tissue microcores and total and diagnostic tissue area.RESULTS: Sixty-four patients were included. The median number of tissue microcores procured per pass was significantly higher in the FNB group compared with FNA (3 vs. 2, P < 0.001). Similarly, the mean total tissue area (2.74 vs. 0.44 mm2, P < 0.001) and mean diagnostic tissue area (1.74 vs. 0.28 mm2, P < 0.001) were more than 6-fold larger in the FNB samples compared with FNA. The median number of passes needed for a diagnostic sample was 1 for the FNB needle and 2 for FNA needle (P = 0.12). The novel FNB needle provided a higher percentage of samples of excellent quality (P = 0.002).CONCLUSIONS: The novel Franseen-type FNB needle seems to be significantly superior to a conventional FNA needle. The results of this study underline excellent performance of crown-cut needles.

Background & Aims Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. Methods All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. Results The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28–5.17; P < .001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58–8.22; P < .001), pancreatic cancer (HR, 6.45; 95% CI, 2.02–20.64; P = .002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76–119.47; P = .013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53–20.23; P = .20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02–3.50; P = .042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. Conclusions Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers., Background & Aims: Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. Methods: All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. Results: The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28–5.17; P <.001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58–8.22; P <.001), pancreatic cancer (HR, 6.45; 95% CI, 2.02–20.64; P =.002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76–119.47; P =.013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53–20.23; P =.20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02–3.50; P =.042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. Conclusions: Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.

Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF–PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies.

Background and aims: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by recurrent epistaxis, telangiectatic lesions in the skin and mucosal membranes, and arteriovenous malformations (AVMs) in various organs. In 3%-5% of patients, HHT is caused by pathogenic germline variants (PVs) in SMAD4, and these patients often have additional symptoms of juvenile polyposis syndrome and thoracic aneurysms. The phenotypic spectrum of SMAD4-associated HHT is less known, including the penetrance and severity of HHT. We aimed to investigate the phenotypic spectrum of HHT manifestations in Danish patients with PVs in SMAD4 and compare the findings with current literature. Methods: The study is a retrospective nationwide study with all known Danish patients with PVs in SMAD4. In total, 35 patients were included. The patients were identified by collecting data from genetic laboratories, various databases and clinical genetic departments across the country. Clinical information was mainly collected from the Danish HHT-Centre at Odense University Hospital. Results: Twenty-nine patients with PVs in SMAD4 (83%) were seen at the HHT-Centre. Seventy-six per cent of these fulfilled the Curaçao criteria, 86% experienced recurrent epistaxis and 83% presented with telangiectatic lesions at different anatomical localisations. Almost 60% had AVMs, mainly pulmonary and hepatic, while none was found to have cerebral AVMs. Fifteen per cent had thoracic aortic abnormalities. Conclusion: We present a nationwide study of one of the largest populations of patients with PVs in SMAD4 that has systematically been examined for HHT manifestations. The patients presented the full spectrum of HHT-related manifestations and the majority fulfilled the Curaçao criteria.