Publications by authors named "John Gásdal Karstensen"

47 Publications

Danish guidelines for management of non-APC-associated hereditary polyposis syndromes.

Hered Cancer Clin Pract 2021 Oct 7;19(1):41. Epub 2021 Oct 7.

Research Unit for Surgery, Odense University Hospital, Odense, Denmark.

Hereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes.
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http://dx.doi.org/10.1186/s13053-021-00197-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499431PMC
October 2021

[New hereditary polyposis syndromes in the patient with intestinal polyps].

Ugeskr Laeger 2021 09;183(38)

Hereditary polyposis syndromes (HPS) are a group of rare, inherited syndromes characterised by the presence of histopathological specific or numerous intestinal polyps and a high risk of intestinal and extraintestinal cancer. During the last decade, several new HPS have been discovered, as it is possible to detect pathogenic germline variants in genes not previously known to be associated with polyposis. This review summarises the current knowledge on the syndromes and discusses genetic testing as part of the diagnostic pipeline when suspecting a polyposis syndrome.
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September 2021

[Videoscopic-assisted retroperitoneal debridement ofnecrotising pancreatitis].

Ugeskr Laeger 2021 07;183(29)

Acute necrotising pancreatitis is a condition associated with high morbidity and mortality, and for decades surgical intervention was the gold standard for treatment of symptomatic pancreatic necrosis. A shift towards minimally invasive interventions has reduced the mortality significantly as summarised in this review. Studies comparing open necrosectomy with videoscopic-assisted retroperitoneal debridement (VARD) have demonstrated that VARD lowers morbidity and mortality. When endoscopic therapy is impossible, VARD is recommended as the preferred surgical intervention for symptomatic necrotising pancreatitis.
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July 2021

EUS-guided biopsy confocal laser endomicroscopy in patients with pancreatic cystic lesions: A systematic review and meta-analysis.

Endosc Ultrasound 2021 Jul-Aug;10(4):270-279

Gastro Unit, Pancreatitis Centre East, Hvidovre Hospital, Hvidovre; Department of Clinical Medicine, University of Copenhagen, København, Denmark.

Background And Objectives: Pancreatic cystic lesions (PCLs) are frequent incidental findings on cross-sectional imaging and represent a diagnostic challenge as different kinds of PCLs harbor a dissimilar risk of malignancy. Two diagnostic tools have recently been developed and introduced: through-the-needle biopsy (TTNB) and needle-based confocal laser endomicroscopy (nCLE). The aim of this meta-analysis was to compare the diagnostic yield and performance, as well as the safety profile of the two methods.

Methods: This meta-analysis was performed in accordance with the PRISMA statement. Medline, Embase, Web of Science, and Cochrane Library databases were searched for studies with five or more patients undergoing either endoscopic ultrasound (EUS)-TTNB or EUS-nCLE for a PCL. Reviews, case reports, editorials, conference abstracts, and studies on exclusively solid pancreatic lesions were excluded. Outcomes of interest were diagnostic yield and performance, safety, and technical success.

Results: Twenty studies with 1023 patients were included in the meta-analysis. Pooled diagnostic yield of EUS-nCLE was higher compared to EUS-TTNB (85% vs. 74%, P < 0.0001), while diagnostic performance was high and comparable for both methods (pooled sensitivity: 80% vs. 86% and pooled specificity: 80% vs. 83% for TTNB and nCLE, respectively, P > 0.05). Pooled estimate of total adverse event (AE) rate was 5% in the TTNB group and 3% in the nCLE group, P = 0.302. Technical success rates were high and comparable (94% and 99% for EUS-TTNB and nCLE, respectively; P = 0.07).

Conclusion: EUS-TTNB and EUS-nCLE have a similar safety profile with a relatively low number of AEs. Technical success, sensitivity, and specificity are comparable; however, EUS-nCLE seems to have a slightly higher diagnostic yield.
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http://dx.doi.org/10.4103/EUS-D-20-00172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411554PMC
July 2021

Deep Learning Algorithm for the Confirmation of Mucosal Healing in Crohn's Disease, Based on Confocal Laser Endomicroscopy Images.

J Gastrointestin Liver Dis 2021 Mar 12;30(1):59-65. Epub 2021 Mar 12.

Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Romania.

Background And Aims: Mucosal healing (MH) is associated with a stable course of Crohn's disease (CD) which can be assessed by confocal laser endomicroscopy (CLE). To minimize the operator's errors and automate assessment of CLE images, we used a deep learning (DL) model for image analysis. We hypothesized that DL combined with convolutional neural networks (CNNs) and long short-term memory (LSTM) can distinguish between normal and inflamed colonic mucosa from CLE images.

Methods: The study included 54 patients, 32 with known active CD, and 22 control patients (18 CD patients with MH and four normal mucosa patients with no history of inflammatory bowel diseases). We designed and trained a deep convolutional neural network to detect active CD using 6,205 endomicroscopy images classified as active CD inflammation (3,672 images) and control mucosal healing or no inflammation (2,533 images). CLE imaging was performed on four colorectal areas and the terminal ileum. Gold standard was represented by the histopathological evaluation. The dataset was randomly split in two distinct training and testing datasets: 80% data from each patient were used for training and the remaining 20% for testing. The training dataset consists of 2,892 images with inflammation and 2,189 control images. The testing dataset consists of 780 images with inflammation and 344 control images of the colon. We used a CNN-LSTM model with four convolution layers and one LSTM layer for automatic detection of MH and CD diagnosis from CLE images.

Results: CLE investigation reveals normal colonic mucosa with round crypts and inflamed mucosa with irregular crypts and tortuous and dilated blood vessels. Our method obtained a 95.3% test accuracy with a specificity of 92.78% and a sensitivity of 94.6%, with an area under each receiver operating characteristic curves of 0.98.

Conclusions: Using machine learning algorithms on CLE images can successfully differentiate between inflammation and normal ileocolonic mucosa and can be used as a computer aided diagnosis for CD. Future clinical studies with a larger patient spectrum will validate our results and improve the CNN-SSTM model.
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http://dx.doi.org/10.15403/jgld-3212DOI Listing
March 2021

Effect and safety of endoscopic sleeve gastroplasty for treating obesity - a systematic review.

Dan Med J 2020 Oct 16;67(11). Epub 2020 Oct 16.

Introduction: Endoscopic sleeve gastroplasty (ESG) represents a novel endoscopic bariatric procedure. It is performed with an endoscope equipped with a suturing device; sutures are placed so that they create a tube-shaped stomach, thereby facilitating weight loss. The aim of this study was to conduct a systematic review evaluating the effectiveness and safety of ESG for treatment of obesity.

Methods: This review was conducted in accordance with the PRISMA guidelines; a protocol was registered with PROSPERO before the start of the study. MEDLINE, Embase and Clinicaltrials.gov were searched through 20 February 2020.

Results: A total of 1,088 articles were assessed. In all, 23 studies met the inclusion criteria. The average total weight loss at 12 months was 16.3%. ESG was associated with a significantly greater weight loss than both intragastric balloon insertion (21.3 ± 6.6 versus 13.9 ± 9.0% total weight loss (TWL) at 12 months, p less than 0.05) and "high-intensity diet and lifestyle therapy" (20.6 ± 8.3 versus 14.3 ± 10.2% TWL at 12 months, p less than 0.05). In contrast, ESG was associated with a significantly lower weight loss than laparoscopic sleeve gastrectomy (17.1 ± 6.5 versus 23.6 ± 7.6% TWL at six months, p less than 0.05). ESG had a significantly lower rate of adverse events than both laparoscopic sleeve gastrectomy (5.2 versus 16.9%, p less than 0.05) and intragastric balloon placement (5.2 versus 17%, p less than 0.05).

Conclusions: ESG is a safe method for treatment of obesity and facilitates a significant weight loss.
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October 2020

Diagnostic performance of current guidelines and postoperative outcome following surgical treatment of cystic pancreatic lesions - a 10-year single center experience.

Scand J Gastroenterol 2020 Dec 4;55(12):1447-1453. Epub 2020 Nov 4.

Gastro Unit, Division of Endoscopy, Herlev Hospital, Herlev, Denmark.

Objective: Pancreatic cystic lesions (PCLs) are diagnostically challenging and there are currently several different guidelines. The aim of this study was to compare diagnostic performance of the most widely utilized International Association of Pancreatology (IAP) guidelines and the recent evidence-based European guidelines and to report on postoperative outcomes following surgical treatment of PCLs.

Methods: This is a retrospective single-center study of patients undergoing surgery due to a PCL between 2010 and 2019. Primary outcome was a comparison of diagnostic performance between IAP and European guidelines, measured in area under the receiver operating characteristic curve (AUC). Other outcomes included diagnostic performance of different risk features, 30-day postoperative mortality and major morbidity, final diagnosis, and overall survival.

Results: We identified 137 patients, three of whom did not undergo curative surgery due to metastatic disease. Overall, there was no difference in the performance of the two guidelines with AUC values ranging from 0.572-0.610 and 0.607-0.621 for IAP and European guidelines respectively. Postoperative 30-day mortality and major morbidity were 0% (95% CI 0.0-2.7%) and 37.3% (95% CI 29.1-46.1%), respectively. More than half of the resected lesions (52.6%) were low-grade dysplastic or non-neoplastic.

Conclusions: Overall, the IAP and the European guidelines performed equally, although European guidelines had a slightly higher mean specificity. Pancreatic surgery is associated with high major morbidity, and there is a need for new diagnostic tools and strategies in order to decrease the amount of overtreatment in patients with PCL.
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http://dx.doi.org/10.1080/00365521.2020.1841283DOI Listing
December 2020

Impact of the COVID-19 pandemic on gastrointestinal endoscopy in Africa.

Endosc Int Open 2020 Aug 7;8(8):E1097-E1101. Epub 2020 Aug 7.

Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy.

As with all other fields of medical practice, gastrointestinal endoscopy has been impacted by the COVID-19 pandemic. However, data on the impact of the pandemic in Africa, especially sub-Saharan Africa are lacking. A web-based survey was conducted by the International Working Group of the European Society for Gastrointestinal Endoscopy and the World Endoscopy Organization to determine the impact and effects the COVID-19 pandemic has had on endoscopists in African countries. Thirty-one gastroenterologists from 14 countries in north, central, and sub-Saharan Africa responded to the survey. The majority of respondents reduced their endoscopy volume considerably. Personal protective equipment including FFP-2 masks were available in almost all participating centers. Pre-endoscopy screening was performed as well. The COVID-19 pandemic has had a substantial impact on gastrointestinal endoscopy in most African countries; however, the impact may not have been as devastating as expected.
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http://dx.doi.org/10.1055/a-1210-4274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413826PMC
August 2020

Endoscopic ultrasound-guided ablation is a promising treatment for pancreatic cystic neoplasms - a systematic review.

Dan Med J 2020 Aug 1;67(8). Epub 2020 Aug 1.

Introduction: With the increasing use of cross-sectional imaging, the incidence of non-symptomatic pancreatic cystic neoplasms is increasing. Surgical management of pancreatic cystic neoplasms possess significant risks of perioperative morbidity and mortality. Our aim was to evaluate endoscopic ultrasound (EUS)-guided ablation as a non-operative treatment of pancreatic cystic neoplasms.

Methods: We performed a literature search in MEDLINE, Embase and Scopus. All clinical studies examining the safety and efficacy of EUS-guided pancreatic cyst ablation with radiofrequency, sclerosants, ethanol, chemotherapeutics or a combination hereof were included.

Results: A total of 17 studies were included. We found that EUS-guided pancreatic cyst ablation was feasible with complete resolution in up to 86% of cases after 3-12 months. The modality with the most promising results after 3-12 months was chemoablation with complete resolution rates ranging from 46 to 79% (median 64%). The most appropriate follow-up period was estimated to be 12 months. The risk of serious adverse events including pancreatitis was approximately 16%. Very few cyst recurrences have been documented following complete resolution after cyst ablation.

Conclusions: EUS-guided cyst ablation of pancreatic cystic lesions seems effective and safe as an alternative to surgical resection in patients who are unfit for surgery or who have low-risk pancreatic cystic neoplasms.
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August 2020

[Endoscopic ultrasound-guided establishment of transmural anastomoses in the upper gastrointestinal tract].

Ugeskr Laeger 2020 07;182(30)

The development of endoscopic ultrasound and lumen-apposing metal stents has resulted in novel therapeutic opportunities with the possibility of establishing a persistent transmural anastomosis for the treatment of multiple gastrointestinal disorders. This review presents the applications and the evidence of endoscopic ultrasound and lumen-apposing metal stents. The modality is an alternative for several upper gastrointestinal disorders. Further research and future technological development will show the final position of this therapy in the current treatment algorithm.
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July 2020

Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cysts.

Endoscopy 2021 Jan 21;53(1):44-52. Epub 2020 Jul 21.

Gastroenterology Unit, Division of Endoscopy, Herlev Hospital, Herlev, Denmark.

Background: The limited data on the utility of endoscopic ultrasound (EUS)-guided through-the-needle biopsies (TTNBs) in patients with pancreatic cystic lesions (PCLs) originate mainly from retrospective studies. Our aim was to determine the clinical impact of TTNBs, their added diagnostic value, and the adverse event rate in a prospective setting.

Methods: This was a prospective, single-center, open-label controlled study. Between February 2018 and August 2019, consecutive patients presenting with a PCL of 15 mm or more and referred for EUS were included. Primary outcome was a change in clinical management of PCLs following TTNB compared with cross-sectional imaging and cytology. Adverse events were defined according to the ASGE lexicon.

Results: 101 patients were included. TTNBs led to a change in clinical management in 11.9 % of cases (n = 12). Of these, 10 had serous cysts and surveillance was discontinued, while one of the remaining two cases underwent surgery following diagnosis of a mucinous cystic neoplasm. The diagnostic yield of TTNBs for a specific cyst diagnosis was higher compared with FNA cytology (69.3 % vs. 20.8 %, respectively;  < 0.001). The adverse event rate was 9.9 % (n = 10; 95 % confidence interval 5.4 % - 17.3 %), with the most common event being acute pancreatitis (n = 9). Four of the observed adverse events were severe, including one fatal outcome.

Conclusions: TTNBs resulted in a change of clinical management in about one in every 10 patients; however, the associated adverse event risk was substantial. Further studies are warranted to elucidate in which subgroups of patients the clinical benefit outweighs the risks.
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http://dx.doi.org/10.1055/a-1214-6043DOI Listing
January 2021

Endoscopic ultrasound-guided gastro-enteric anastomosis: A systematic review and meta-analysis.

Dig Liver Dis 2020 11 3;52(11):1294-1301. Epub 2020 Jun 3.

Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Denmark.

Background And Aims: Endoscopic ultrasound-guided gastro-enteric anastomosis (EUS-GEA) using lumen-apposing metal stents (LAMS) is emerging as a minimally invasive alternative to surgery across several indications. Literature on this subject is heterogeneous, with variable reporting of techniques and outcomes. Our aim was to perform a meta-analysis of published data on EUS-GEA, providing a pooled estimate of technical and clinical outcomes.

Methods: The protocol was registered in PROSPERO (Reg. no. CRD42018111110). PubMed, Embase, Scopus, and Web of Science databases were searched until February 2019 for studies describing patients undergoing EUS guided enteric anastomosis. PRISMA methodology was used. Pooled technical and clinical success rates as well as pooled adverse events rates were calculated. Study quality, publication bias, and heterogeneity were explored.

Results: Twelve studies including 290 patients were included, published between 2016 and 2019. All studies but one were retrospective. Main procedure indication was gastric outlet obstruction (62.4%), followed by ERCP access (27.9%) in patients with gastric bypass surgery. Direct puncture technique was the most frequently adopted (68.2%). Pooled technical success rate (12 studies, 290 patients) was 93.5% [95% confidence interval (CI) 89.7-6.0%; I:0%], while clinical success rate (11 studies, 260 patients) was 90.1% [95%CI 85.5-93.4%; I:0%]. Pooled total adverse events rate (11 cohorts, 261 patients) was 11.7% [95%CI 8.2-16.6%; I:0%], mainly mild/moderate: 10.6% [95%CI 7 - 15.6%]. No publication bias or significant heterogeneity was found.

Conclusions: EUS-GEA has a high rate of technical and clinical success when performed in expert centers. The procedure appears to be relatively safe, and might represent a non-inferior minimally invasive alternative to surgery. The paucity of long-term clinical outcomes suggests prudency and need for further research, especially regarding non-malignant indications.
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http://dx.doi.org/10.1016/j.dld.2020.04.021DOI Listing
November 2020

Two cases of somatic STK11 mosaicism in Danish patients with Peutz-Jeghers syndrome.

Fam Cancer 2021 01 6;20(1):55-59. Epub 2020 Jun 6.

Danish Polyposis Registry, Hvidovre Hospital, Gastrounit, Hvidovre, Denmark.

Peutz-Jeghers syndrome (PJS) is a hereditary polyposis syndrome characterized by hamartomatous Peutz-Jeghers polyps in the gastrointestinal tract, mucocutaneous pigmentations, and increased risk for intestinal and extraintestinal cancer. In more than two-third of patients it is possible to detect pathogenic variants in the serine/threonine kinase 11 (STK11) gene, but so far is knowledge about genetic causes in the remaining part of patients limited. Reports of STK11 mosaicism are rare but may be an explanation in some patients without initial findings of pathogenic variants in STK11. We report two Danish patients with STK11 mosaicism detected in blood when using Next-Generation Sequencing. This is only the sixth and seventh patient reported in the literature, and we compare phenotypes of the reported cases. The results indicate that STK11 mosaicism is more frequent than anticipated and highlight that mosaicism should be considered in patients with clinical suspicion of PJS or patients fulfilling the diagnostic criteria.
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http://dx.doi.org/10.1007/s10689-020-00191-4DOI Listing
January 2021

Coronavirus Disease-19 (COVID-19) associated with severe acute pancreatitis: Case report on three family members.

Pancreatology 2020 Jun 5;20(4):665-667. Epub 2020 May 5.

Pancreatitis Centre East, Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.

Background/objectives: Abdominal pain is one of the known symptoms associated with coronavirus disease 2019. Little is known about the development of acute pancreatitis as a complication of severe acute respiratory syndrome coronavirus 2 infection. This case report describes the presentation of acute pancreatitis in two of three family members with severe COVID-19 infection.

Methods: Data were collected from three family members admitted with COVID-19 to the intensive care unit in March 2020. This study was reviewed and approved by the local data and ethics committee (31-1521-253).

Results: Two of the three family members were diagnosed with acute pancreatitis associated with SARS-CoV-2. Other causes of acute pancreatitis were excluded for both patients (including alcohol, biliary obstruction/gall stones, drugs, trauma, hypertriglyceridemia, hypercalcemia, and hypotension).

Conclusions: These cases highlight acute pancreatitis as a complication associated with COVID-19 and underlines the importance of measuring pancreas-specific plasma amylase in patients with COVID-19 and abdominal pain.
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http://dx.doi.org/10.1016/j.pan.2020.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199002PMC
June 2020

DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis.

Endosc Ultrasound 2020 Jan-Feb;9(1):37-44

Division of Endoscopy, Gastro Unit, Copenhagen University Hospital, Herlev, Denmark.

Background And Objectives: EUS-FNA is inconclusive in up to 10%-15% of patients with solid pancreatic lesions (SPLs). We aimed to investigate whether supplementary genetic analyses with whole-exome sequencing add diagnostic value in patients with SPLs suspicious of malignancy but inconclusive EUS-FNA.

Patients And Methods: Thirty-nine patients, who underwent EUS-FNA of an SPL were retrospectively included. Three groups were defined: 16 (41.0%) had suspected malignancy on EUS confirmed by cytology (malignant), 13 (33.3%) had suspected malignancy on EUS but benign cytology (inconclusive), and 10 (25.6%) had benign EUS imaging and cytology (benign). Areas with the highest epithelial cell concentrations were macro-dissected from the FNA smears from each patient, and extracted DNA was used for whole-exome sequencing by next-generation sequencing of a selected gene panel including 19 genes commonly mutated in cancer.

Results: Pathogenic mutations in K-RAS, TP53, and PIK3CA differed significantly between the three groups (P < 0.001, P = 0.018, and P = 0.026, respectively). Pathogenic mutations in KRAS and TP53 were predominant in the inconclusive (54% and 31%, respectively) and malignant groups (81.3% and 50%, respectively) compared to the benign group (0%). Malignant and inconclusive diagnoses correlated strongly with poor overall survival (P < 0.001).

Conclusion: Whole-exome sequencing of genes commonly mutated in pancreatic cancer may be an important adjunct in patients with SPLs suspicious for malignancy on EUS but with uncertain cytological diagnosis.
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http://dx.doi.org/10.4103/eus.eus_36_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038737PMC
September 2019

[Diagnostic investigation, treatment and follow-up of pancreatic cysts].

Ugeskr Laeger 2019 Jun;181(23)

Pancreatic cancer has a low five-year survival rate, which in part is due to late recognition of the disease making surgical intervention impossible. Some pancreatic cancers stem from cystic lesions. The expanded use of advanced diagnostic imaging like CT and MRI has led to an increase in incidental and potentially malignant pancreatic cysts. This review presents the newest international guidelines and gives a Danish perspective in order to increase knowledge on how to deal with incidental pancreatic cysts as regards further diagnostic investigation, treatment and follow-up.
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June 2019

Colorectal Cancer in Individuals With Familial Adenomatous Polyposis, Based on Analysis of the Danish Polyposis Registry.

Clin Gastroenterol Hepatol 2019 10 8;17(11):2294-2300.e1. Epub 2019 Feb 8.

Danish Polyposis Registry, Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

Background & Aims: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that increases risk for colorectal cancer (CRC). We assessed changes in the incidence and prevalence of CRC, and survival times, of patients with FAP participating in the Danish follow-up study.

Methods: We collected data from the Danish Polyposis Registry, a nationwide, complete registry of patients with FAP that includes clinical information, surgical procedures, follow-up findings, and pathology reports. We compared data between the periods of 1990-1999 and 2000-2017. In 2017, the registry contained 226 families with 721 individuals with FAP. Probands were defined as patients diagnosed based on bowel symptoms, without any knowledge of hereditary bowel disease. Call-up patients were defined as those found to have FAP during screening and due to a diagnosis of FAP in first-degree relatives.

Results: Although the mean incidence rate of FAP was stable from 1990-1999 (0.19/100,000/year) to 2000-2017 (0.32/100,000/year) (P = .91), the point prevalence increased from 4.86/100,000 in 1999 to 6.11/100,000 by the end of 2017 (P = .005). During 2000-2017, 25 of 72,218 CRC cases were associated with FAP (0.03%)-this was a significant decrease from 1990-1999 (26/30,005 cases; 0.09%) (P = .001). The risk of CRC was significantly higher for probands (n = 191; 61.6%) than call-up cases (n = 5; 1.9%) (P < .001). All CRCs in call-up patients were detected at the diagnosis of FAP (no cases were identified in the follow-up program). The median life expectancy for call-up patients was 72.0 years (95% CI, 63.3-80.7), compared to 55.0 years for probands (95% CI, 51.2-58.8) (P < .001). Therefore, the tracing and follow-up program increased life expectancy by 17.0 years for first-degree family members.

Conclusion: The Danish Polyposis Registry enables close monitoring of patients with FAP, reducing risk of CRC and prolonging life.
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http://dx.doi.org/10.1016/j.cgh.2019.02.008DOI Listing
October 2019

Subtyping of intraductal papillary mucinous neoplasms - pitfalls of MUC1 immunohistochemistry.

APMIS 2019 Jan 22;127(1):27-32. Epub 2018 Nov 22.

Department of Pathology, Copenhagen University Hospital Rigshospitalet, København, Denmark.

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN-lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.
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http://dx.doi.org/10.1111/apm.12900DOI Listing
January 2019

Efficacy of Endoscopic Dilation of Gastroduodenal Crohn's Disease Strictures: A Systematic Review and Meta-Analysis of Individual Patient Data.

Clin Gastroenterol Hepatol 2019 11 29;17(12):2514-2522.e8. Epub 2018 Nov 29.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Background & Aims: Little is known about the effects of endoscopic balloon dilation (EBD) for strictures of the upper gastrointestinal (UGI) tract in patients with Crohn's disease (CD). We performed a pooled analysis of the efficacy and safety of EBD for UGI CD-associated strictures.

Methods: We searched Embase, Medline, and the Cochrane library, as well as bibliographies of relevant articles, for cohort studies of adults with CD and strictures of the stomach or duodenum (up to the ligament of Treitz) who underwent EBD through December 2016. We obtained data from 7 international referral centers on 94 patients who underwent 141 EBDs. We performed a patient-level meta-analysis of data from published and unpublished cohort studies to determine mechanical and clinical success. We performed a time-to-event analysis to assess symptom recurrence and need for redilation or surgery. The patients analyzed had strictures of the duodenum (n = 107), stomach (n = 30), or spanning both (n = 4).

Results: The rate of technical success for EBD was 100%, with 87% short-term clinical efficacy; major complications arose from 2.9% of all procedures. During a median follow-up period of 23.1 months, 70.5% of patients had a recurrence of symptoms, 59.6% required redilation, and 30.8% required surgical intervention. Patients whose disease was located in the small bowel had a higher risk for symptom recurrence (hazard ratio [HR], 2.1; P = .003). Asian race (HR, 2.8; P < .001) and location of disease in the small bowel (HR, 1.9; P = .004) increased the need for redilation. Prestenotic dilation was a risk factor for needing surgery earlier (HR, 1.9; P = .001).

Conclusions: In a meta-analysis, we found EBD for CD-associated strictures of the UGI to be an effective alternative to surgery, with a high rate of short-term technical and clinical success, moderate long-term efficacy, and an acceptable rate of complications.
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http://dx.doi.org/10.1016/j.cgh.2018.11.048DOI Listing
November 2019

Partnership with African Countries: European Society of Gastrointestinal Endoscopy (ESGE) - Position Statement.

Endosc Int Open 2018 Oct 8;6(10):E1247-E1255. Epub 2018 Oct 8.

Gastroenterology and Endoscopy, Edouard Herriot Hospital, Lyon, France.

A new objective for the European Society of Gastrointestinal Endoscopy (ESGE) is to develop long-term partnerships with African countries. For this, an International Affairs Working Group (IAWG) was formed. In conjunction with the World Endoscopy Organization (WEO), ESGE conducted a survey of gastrointestinal (GI) endoscopy in Africa. Survey results showed that many African countries have few GI endoscopy centers with adequate resources. Barriers to the development of endoscopy services include a shortage of endoscopists who have undergone advanced endoscopy training, and a lack of equipment and basic infrastructure. Diseases related to infectious etiology are more prevalent than neoplastic diseases in Africa. Any development of endoscopy services needs to consider the local prevalence of diseases for which GI endoscopy is required, as well as the availability of resources. The IAWG will initiate a cascade approach to identify and adapt ESGE guidelines for local use. The guidelines will consider the level of resources available for each intervention, as well as cost, infrastructure, and training, and will be approved by consensus of local experts who are representative of different African areas. Suitable centers in African countries will be identified, and in future will be developed into WEO/ESGE training centers, to provide local training in both basic and advanced endoscopy according to the needs of the area.
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http://dx.doi.org/10.1055/a-0677-2026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175688PMC
October 2018

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

Gastrointest Endosc 2019 03 28;89(3):545-553. Epub 2018 Sep 28.

Gastroenterology and Liver Institute, Laniado Hospital, Netanya, Israel; Department of Gastroenterology and Hepatology, UMC Radboud, Nijmegen, Netherlands.

Background And Aims: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR.

Methods: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR.

Results: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026).

Conclusion: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).
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http://dx.doi.org/10.1016/j.gie.2018.09.028DOI Listing
March 2019

Initial experience with EUS-guided microbiopsy forceps in diagnosing pancreatic cystic lesions: A multicenter feasibility study (with video).

Endosc Ultrasound 2018 Nov-Dec;7(6):383-388

Division of Endoscopy, Gastro Unit, Copenhagen University Hospital Herlev, Copenhagen, Denmark.

Background And Objectives: Cystic lesions of the pancreas represent a diagnostic dilemma. Recently, a through-the-needle microbiopsy forceps has become available, enabling procurement of EUS-guided histological specimens from the pancreatic cyst wall. The aim of this study was to evaluate the use of this novel instrument in a multicenter clinical setting.

Patients And Methods: Patients referred for EUS evaluation of pancreatic cysts and attempted EUS-guided microbiopsy was included retrospectively from six international tertiary centers. Patient's demographics, EUS findings, technical and clinical success, and histopathological results were recorded.

Results: : A total of 28 patients were identified. We report a technical success rate of 85.7% (n = 24). Biopsies were generally of good quality and contributed to the diagnosis in 20 patients (clinical success of 71.4%). Three adverse events were recorded (10.7%).

Conclusions: The use of the microbiopsy forceps is feasible with acceptable rates of technical and clinical success. Prospective studies are warranted to determine the diagnostic potential compared to the other modalities. However, the results from this preliminary study are promising.
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http://dx.doi.org/10.4103/eus.eus_16_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289018PMC
September 2018

Diagnosis of intraductal papillary mucinous neoplasm using endoscopic ultrasound guided microbiopsies: A case report.

World J Gastrointest Endosc 2018 Jul;10(7):125-129

Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev and Gentofte, Herlev 2730, Denmark.

Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging, but current diagnostic modalities have limited diagnostic accuracy. Recently, a novel through-the-needle microbiopsy forceps has become available, offering the possibility of obtaining cyst-wall biopsies. We present a case of 41-year-old male with chronic pancreatitis and a 2-cm pancreatic cyst, initially considered a pseudocyst. Subsequently, endoscopic ultrasound guided microbiopsies were successfully obtained, which surprisingly revealed an intraductal papillary mucinous neoplasm of mixed subtype with low grade dysplasia. In conclusion, obtaining biopsies from the wall of the pancreatic cystic lesions with this novel instrument is feasible and, as demonstrated in this case, can possibly alter the clinical outcome. Microbiopsies offered enough cellular material, allowing supplemental gene mutation analysis, which combined with other modalities could lead to a more individual approach when treating pancreatic cysts. However, prospective studies are warranted before routine clinical implementation.
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http://dx.doi.org/10.4253/wjge.v10.i7.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068726PMC
July 2018

A novel endoscopic ultrasound-guided through-the-needle microbiopsy procedure improves diagnosis of pancreatic cystic lesions.

Endoscopy 2018 11 6;50(11):1105-1111. Epub 2018 Jul 6.

Gastro Unit, Division of Endoscopy, Copenhagen University Hospital, Herlev, Denmark.

Background: Pancreatic cystic lesions represent a diagnostic dilemma as some may harbor malignancy or have potential for malignant transformation. The aim of this study was to present our experience with a novel endoscopic ultrasound (EUS)-guided microbiopsy procedure enabling procurement of tissue from the wall of the cystic lesion.

Methods: We collected data from 31 consecutive patients with pancreatic cystic lesions who underwent an EUS-guided microbiopsy procedure at our institution. Records were retrospectively reviewed from a prospectively maintained database.

Results: The technical success was 87.1 %. Diagnostic yield of microbiopsies was 71.0 %. Microbiopsies offered sufficient tissue for morphological and immunohistochemical characterization of the lesions, as well as determination of grade of dysplasia. Furthermore, evaluation of microbiopsies changed the clinical management in six patients (19.4 %). Three nonsevere adverse events were observed (9.7 %): two cases of mild infection and one case of mild pancreatitis. All three patients recovered completely.

Conclusions: EUS-guided microbiopsy procedure was technically feasible, with a high diagnostic yield. Further prospective studies are needed to confirm these promising results.
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http://dx.doi.org/10.1055/a-0625-6440DOI Listing
November 2018

SMAD4 Protein Expression Is Downregulated in Ileal Epithelial Cells from Patients with Crohn's Disease with Significant Inverse Correlation to Disease Activity.

Gastroenterol Res Pract 2018 24;2018:9307848. Epub 2018 May 24.

Department of Pathology, Copenhagen University Hospital Herlev and Gentofte, DK-2730 Herlev, Denmark.

Background: Small mothers against decapentaplegic (SMAD)4 and SMAD7 are key regulatory components in the immunosuppressive transforming growth factor- (TGF-) signaling pathway, which is defective in inflammatory bowel disease (IBD). SMAD4 may play an important role in the pathogenesis of IBD as indicated in experimental models of colitis.

Aims: To examine the ileal expression levels of SMAD4 and to correlate these with CD disease activity.

Methods: The material comprised 29 CD patients (13 with active disease, 16 in remission) and 9 asymptomatic patients referred for ileocolonoscopy as part of an adenoma surveillance program serving as controls. Patients were examined with ileocolonoscopy. Corresponding ileal biopsies were obtained for histological analysis and assessment of SMAD4 and SMAD7 protein expression by immunohistochemistry (IHC).

Results: The protein expression of SMAD4 was significantly downregulated in ileal tissue sections from CD patients as compared to healthy controls ( < 0.001). Further, luminal SMAD4 expression was inversely correlated with endoscopic ( = -0.315; = 0.05) and histopathological activity ( = -0.40; = 0.013).

Conclusions: The SMAD4 epithelial protein level was markedly downregulated in CD patients and inversely correlated with disease activity. This may contribute to defective mucosal TGF- signaling in active IBD.
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http://dx.doi.org/10.1155/2018/9307848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994270PMC
May 2018
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