Search

Anne Marie Jelsig,1 Anna Byrjalsen,1 Majbritt Busk Madsen,2 Tine Plato Kuhlmann,3 Thomas van Overeem Hansen,1 Karin AW Wadt,1,4 John Gásdal Karstensen4,5 1Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark; 2Center for Genomic Medicine, University Hospital of Copenhagen, Copenhagen, Denmark; 3Department of Pathology, University Hospital of Copenhagen, Herlev Hospital, Herlev, Denmark; 4Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 5Danish Polyposis Registry, Gastro Unit, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, DenmarkCorrespondence: Anne Marie JelsigDepartment of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, DenmarkTel +45 20 36 18 85Email anne.marie.jelsig@regionh.dkAbstract: Hereditary polyposis syndromes are characterized by a large number and/or histopathologically specific polyps in the gastrointestinal tract and a high risk of both colorectal cancer and extracolonic cancer at an early age. While the genes responsible for some of the syndromes, eg, APC in familial adenomatous polyposis and STK11 in Peutz-Jeghers syndrome, have been known for decades, novel genetic causes have recently been detected that have shed light on the broader clinical spectrum of syndromes. Genetic diagnoses are important because they can facilitate a personalized surveillance program. Furthermore, at-risk members of the patient’s family can be tested and enrolled in surveillance as needed. In some cases, prenatal diagnostics should be offered. In this paper, we describe the development in germline genetics of the hereditary polyposis syndromes over the last 10– 12 years, their clinical characteristics, as well as how to implement genetic analyses in the diagnostic pipeline.Keywords: polyposis, hereditary, familial adenomatous polyposis, cancer, management

Introduction: Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene. FAP is usually categorized according to phenotype: classical FAP (CFAP) and attenuated FAP (AFAP); the latter is considered to have a milder disease course. We aimed to assess the risk of overall and specific cancers in patients with CFAP and AFAP compared with matched, nonexposed individuals., Methods: All known Danish patients with FAP were classified as either CFAP or AFAP and assigned 4 matched, nonexposed individuals. The risk of overall and specific cancers, and mortality were analyzed., Results: The analysis included 311 patients with CFAP, 134 patients with AFAP, and 1,600 nonexposed individuals. The overall cancer risk was significantly higher for both patients with CFAP and AFAP than for nonexposed individuals, with hazard ratios (HRs) of 4.77 (95% confidence interval [CI], 3.61-6.32; P < 0.001) for CFAP and 3.22 (95% CI, 2.16-4.80; P < 0.001) for AFAP. No significant difference was observed when comparing CFAP and AFAP (HR = 1.48; 95% CI, 0.98-2.25; P = 0.0646). The HR of colonic cancer was 2.16 (95% CI, 0.99-7.72; P = 0.0522) and 2.72 (95% CI, 1.19-6.22; P = 0.0177 for CFAP and AFAP), respectively, compared with nonexposed and did not differ between patients with CFAP and AFAP (HR = 0.80; 95% CI, 0.32-2.00; P = 0.6278). Mortality was significantly higher in CFAP (HR = 2.96; 95% CI, 2.04-4.28; P < 0.001), but not in AFAP (HR = 1.40; 95% CI, 0.73-2.69; P = 0.311)., Discussion: Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared with nonexposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway., Methods: We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010-2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR)., Results: We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84]., Conclusion: In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aims to evaluate the developments in the testing of Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations across different cancer types and regions in Denmark from 2010 to 2022., Study Design and Setting: Using comprehensive data from the Danish health registries, we linked molecular test results from the Danish Pathology Registry with cancer diagnoses from the Danish National Patient Registry between 2010 and 2022. We assessed the frequency and distribution of KRAS and BRAF mutations across all cancer types, years of testing, and the five Danish regions., Results: The study included records of KRAS testing for 30 671 patients and BRAF testing for 30 860 patients. Most KRAS testing was performed in colorectal (78%) and lung cancer (18%), and BRAF testing in malignant melanoma (13%), colorectal cancer (67%), and lung cancer (12%). Testing rates and documentation mutational subtypes increased over time. Reporting of wildtype results varied between lung and colorectal cancer, with underreporting in lung cancer. Regional variations in testing and reporting were observed., Conclusion: Our study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach., (© 2024 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Background and study aims Colorectal serrated lesions and polyps (SPs) include hyperplastic polyps (HP), sessile serrated lesions-/+dysplasia (SSL/SSL-D), and traditional serrated adenomas (TSA). From 20% to 30% of colorectal cancers (CRC) develop from SP. We present incidence and baseline characteristics of SP in a Danish cohort. Patients and methods We used The Danish Pathology Registry to include all SPs in the Danish population from January 1, 2000 to December 31, 2021. Based on the unique Danish personal identification number and SNOMED-codes, combined with the age and sex of patients, and date of procedure, we determined the incidence of the SP subtypes, anatomical location, and changes over time. Results During the period from 2000 to 2021, a total of 292,761 SPs were removed from 163,840 patients: 51,649 SSLs, 5959 SSL-Ds, 224,860 HDs, and 10,293 TSAs. The median age of patients was 64.1 years (range 55.2-71.6) and 53.3% were male. We found a general increase in SPs from 3525 in 2000 to 25,853 in 2021 and a rise in the SSL proportion from 1.7% in 2006 to 38% in 2021. Half of all patients had more than one lesion at endoscopy with conventional adenomas being the most common. CRC was found along with SPs in 3.3% of procedures, while 1% to 2.5% of the patients developed metachronous CRC. Conclusions We found an increasing number of SPs, especially SSLs. From 2019 to 2021 the number of SPs seem to stabilize, while the proportion of SSLs keeps rising. Synchronous lesions were common along all subtypes of SP., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Risk assessment of disease recurrence in pT1 colorectal cancer is crucial in order to select the appropriate treatment strategy. The study aimed to develop a prediction model, based on histopathological data, for the probability of disease recurrence and residual disease in patients with pT1 colorectal cancer., Methods: The model dataset consisted of 558 patients with pT1 CRC who had undergone endoscopic resection only (n = 339) or endoscopic resection followed by subsequent bowel resection (n = 219). Tissue blocks and slides were retrieved from Pathology Departments from all regions in Denmark. All original slides were evaluated by one experienced gastrointestinal pathologist (TPK). New sections were cut and stained for haematoxylin and eosin (HE) and immunohistochemical markers. Missing values were multiple imputed. A logistic regression model with backward elimination was used to construct the prediction model., Results: The final prediction model for disease recurrence demonstrated good performance with AUC of 0.75 [95% CI 0.72-0.78], HL chi-squared test of 0.59 and scaled Brier score of 10%. The final prediction model for residual disease demonstrated medium performance with an AUC of 0.68 [0.63-0.72]., Conclusion: We developed a prediction model for the probability of disease recurrence in pT1 CRC with good performance and calibration based on histopathological data. Together with lymphatic and venous invasion, an involved resection margin (0 mm) as opposed to a margin of ≤ 1 mm was an independent risk factor for both disease recurrence and residual disease., (© 2023. The Author(s).)

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., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Transanal endoscopic microsurgery (TEM) represents a choice of treatment in patients with neoplastic lesions in the rectum. When TEM fails, completion total mesorectal excision (cTME) is often required. However, a concern is whether cTME increases the rate of abdominoperineal resections (APR) and is associated with higher risk of incomplete mesorectal fascia (MRF) resection. The aim of this study was to compare outcomes of cTME with primary TME (pTME) in patients with rectal cancer., Methods: This was a nationwide study on all patients with cTME from the Danish Colorectal Cancer Group database between 2005 and 2015. Patients with cTME were compared to patients with pTME after propensity score matching (matching ratio 1:2). Matching variables were age, gender, tumor distance from anal verge, American Society of Anesthesiologists (ASA) score and American Joint Committee on Cancer (AJCC) stage., Results: A total of 60 patients with cTME were compared with 120 patients with pTME. Patients with cTME experienced more intraoperative complications as compared to pTME patients (18.3% vs. 6.7%, p = 0.021). However, there was no difference in the rate of perforations at or near the tumor/previous TEM site (6.7% vs. 2.5%, p = 0.224), conversion to open surgery (p = 0.733) or 30-day morbidity (p = 0.86). On multivariate analysis, cTME was not a risk factor for APR (OR 2.49; 95% CI 0.95-6.56; p = 0.064) or incomplete MRF (OR 1.32; 95% CI 0.48-3.63; p = 0.596). There was no difference in the rate of local recurrence between cTME and pTME (5.2% vs. 4.3%, p = 0.1), distant metastases (6.8% vs. 6.8%, p = 1), or survival (p = 0.081). The mean follow-up time was 6 years., Conclusion: In our study, the largest so far on the subject, we find no difference in postoperative short- or long-term outcomes between cTME and pTME., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Context.—: Errors in laboratory medicine could compromise patient safety. Good laboratory practice includes identifying and managing nonconformities in the total test process. Varying error percentages have been described in other fields but are lacking for molecular oncology., Objectives.—: To gain insight into incident causes and frequency in the total test process from 8 European institutes routinely performing biomarker tests in non-small cell lung cancer and colorectal cancer., Design.—: All incidents documented in 2018 were collected from all hospital services for pre-preanalytical entries before the biomarker test, as well as specific incidents for biomarker tests., Results.—: There were 5185 incidents collected, of which 4363 (84.1%) occurred in the pre-preanalytical phase (all hospital services), 2796 of 4363 (64.1%) related to missing or incorrect request form information. From the other 822 specific incidents, 166 (20.2%) were recorded in the preanalytical phase, 275 (33.5%) in the analytical phase, and 194 (23.6%) in the postanalytical phase, mainly due to incorrect report content. Only 47 of 822 (5.7%) incidents were recorded in the post-postanalytical phase, and 123 (15.0%) in the complete total test process. For 17 of 822 (2.1%) incidents the time point was unknown. Pre-preanalytical incidents were resolved sooner than incidents on the complete process (mean 6 versus 60 days). For 1215 of 5168 (23.5%) incidents with known causes a specific action was undertaken besides documenting them, not limited to accredited institutes., Conclusions.—: There was a large variety in the number and extent of documented incidents. Correct and complete information on the request forms and final reports are highly error prone and require additional focus.

Tumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines. With the wider reporting of tumor budding, new issues have emerged that require further clarification. To better inform researchers and health-care professionals on these issues, an international group of experts in gastrointestinal pathology participated in a modified Delphi process to generate consensus and highlight areas requiring further research. This effort serves to re-affirm the importance of tumor budding in colorectal cancer and support its continued use in routine clinical practice., (© 2021. The Author(s).)

Aims: Results from external quality assessment revealed considerable variation in neoplastic cell percentages (NCP) estimation in samples for biomarker testing. As molecular biology tests require a minimal NCP, overestimations may lead to false negative test results. We aimed to develop recommendations to improve the NCP determination in a prototypical entity - colorectal carcinoma - that can be adapted for other cancer types., Methods and Results: A modified Delphi study was conducted to reach consensus by 10 pathologists from 10 countries with experience in determining the NCP for colorectal adenocarcinoma. This study included two online surveys and a decision-making meeting. Consensus was defined a priori as an agreement of > 80%. All pathologists completed both surveys. Consensus was reached for 8 out of 19 and 2 out of 13 questions in the first and second surveys, respectively. Remaining issues were resolved during the meeting. Twenty-four recommendations were formulated. Major recommendations resulted as follows: only pathologists should conduct the morphological evaluation; nevertheless molecular biologists/technicians may estimate the NCP, if specific training has been performed and a pathologist is available for feedback. The estimation should be determined in the area with the highest density of viable neoplastic cells and lowest density of inflammatory cells. Other recommendations concerned: the determination protocol itself, needs for micro- and macro-dissection, reporting and interpreting, referral practices and applicability to other cancer types., Conclusion: We believe these recommendations may lead to more accurate NCP estimates, ensuring the correct interpretation of test results, and might help in validating digital algorithms in the future., (© 2019 The Authors. Histopathology Published by John Wiley & Sons Ltd.)

Unlabelled: Growing evidence from data base and laboratory studies demonstrates effective occupant protection with the airbag supplemental restraint and seatbelt restraint system. Concern that drivers of vehicles equipped with airbags may assume adequate protection without concomitant seatbelt use prompted the study of unbelted occupant behavior in frontal crashes., Objective: To evaluate the crash protection afforded unbelted drivers in airbag-equipped vehicles., Design: Six laboratory sled tests were conducted with a production driver's side airbag and knee bolster restraint system but without a seatbelt restraint system., Materials and Methods: Four human cadavers and the Hybrid III dummy were used as occupants in 32 km/h and 48 km/h tests with a simulated mid-size vehicle., Measurements and Main Results: Head contact with the windshield/header region of the simulated vehicle and abdominal impingement on the lower rim of the steering wheel were noted in all tests. Autopsy examinations and radiographic images identified extensive spinal and thoracic trauma in addition to lower extremity and facial injuries. Injury Severity Scores were considered severe to critical for all occupants., Conclusions: The evidence suggests the need to emphasize the use of seatbelts in conjunction with airbags and to develop a redesigned airbag and knee bolster system to control occupant kinematics and loading more effectively.

Study Objective: To assess the perceived impact of emergency medicine residency programs on other program directors' perceptions of emergency medicine as a distinct service and educational entity., Design: Self-administered questionnaire., Type of Participants: Residency directors in medicine, surgery, pediatrics, and obstetrics and gynecology at sites containing emergency medicine residency programs., Results: Two hundred twenty-four of 372 questionnaires (60.1%) were returned completed, with equal distributions among all specialties. Respondents stated that the presence of the emergency medicine training program has positively influenced their attitude toward emergency medicine as a specialty (61% agree, 26% neutral), improved their residents' training in emergency medicine (47% agree, 31% neutral), and improved emergency care at their institution (65% agree, 26% neutral). Fifty-seven percent think emergency physicians should teach emergency medicine (27% were neutral). There were statistically significant associations between age of the emergency medicine program and perceived improvement in rotating residents' education and institutional delivery of emergency care., Conclusion: Residency directors in other specialties have a generally positive view of emergency medicine as a specialty and as an important component of their residents' education. The presence of an emergency medicine training program appears to have positively influenced their attitudes, improved their residents' education, and improved emergency care. Older programs have positively influenced attitudes to a greater degree than have newer programs.

Study Objective: To determine if light reflection rheography is a useful screening tool for the diagnosis of proximal leg deep venous thrombosis., Design: Light reflection rheography was compared with duplex ultrasonography and/or contrast venography on emergency patients being evaluated for proximal leg deep venous thrombosis., Setting: University hospital emergency department., Type of Participants: Seventy-five ED patients being evaluated for acute leg deep venous thrombosis., Interventions: Seventy-five patients being evaluated for clinically suspected deep venous thrombosis had light reflection rheography performed on the involved extremity immediately before duplex ultrasonography and/or contrast venography. Duplex ultrasonography and/or contrast venography was the definitive diagnostic test., Measurements and Results: Seventy-five patients had light reflection rheography performed, 72 had duplex ultrasonography, 19 had contrast venography, three had contrast venography alone, and 16 had both duplex ultrasonography and contrast venography. A comparison of light reflection rheography with duplex ultrasonography and/or contrast venography reveals that 39 light reflection rheography examinations were true-negative, 17 were true-positive, one was false-negative, and 18 were false-positive. The sensitivity of light reflection rheography for the detection of proximal leg deep venous thrombosis is 94.4% (95% confidence interval [CI], 72.7-99.9%), the negative-predictive value is 97.5% (95% CI, 86.8-99.9%), the specificity is 68.4% (95% CI, 54.8-80.1%), and the positive-predictive value is 48.6% (95% CI, 31.4-66%)., Conclusion: Light reflection rheography proved to be an excellent screening tool for emergency patients with the clinical suspicion for an acute proximal leg deep venous thrombosis. A normal light reflection rheography examination was 97.5% accurate as a negative predictor. That is, a normal light reflection rheography excluded the diagnosis of proximal leg deep venous thrombosis when compared with duplex ultrasonography and/or contrast venography when the duplex ultrasonography and/or contrast venography showed no evidence of proximal leg deep venous thrombosis. An abnormal light reflection rheography does not equate to an acute leg deep venous thrombosis as the specificity was only 68.4%. An abnormal light reflection rheography mandates further diagnostic studies such as duplex ultrasonography and/or contrast venography to confirm a diagnosis of proximal leg deep venous thrombosis.

The nature of the first year of postgraduate medical education has gone through many changes over the years. Relatively recent changes have made this first year into a specialty-specific experience. Medical students are increasingly experiencing a narrowed and less broad-based clinical education. Many students, residents, and attending physicians complain that they wish they had had a "rotating" or "flexible" internship. Graduate medical education authorities have recently recommended that the internship year return to a broad-based general medical education experience. In 1989, the authors surveyed the entire physician faculty and housestaff at a large academic health sciences center, asking them what type of first postgraduate year (PGY-1) the physicians had experienced themselves and what type of PGY-1 they recommended for future graduating medical students. Over one-third strongly recommended that the PGY-1 should be broad-based and not specialty-specific.

Injuries to front seat occupants in tow-away crashes in the Charlottesville, Va, area were compared for 1 year before and 1 year after Virginia's seat belt use law took effect. Vehicle and occupant data were combined to examine crash and injury patterns. Reported seat belt use in crashes increased after the law, and there were substantial decreases in injuries. Front seat occupants were less likely to receive medical treatment following a crash in the postlaw period. The reduction in the number of injuries was greater for passengers in the right front seat than for drivers and for frontal crashes than for other types of crashes. The injury reduction effects occurred primarily through reductions in the number of head and face injuries, particularly those that occur from contact with windshields and instrument panels.

Presented is a case of syncope as the initial sign of a painless aortic dissection. The patient was stabilized by percutaneous drainage of a hemopericardium, and then underwent angiography and successful operative repair. Although uncommon, painless aortic dissection should be included in the differential diagnosis of a syncopal episode.

A rhytidectomy incision is recommended to excise multiple facial epidermal cysts in patients with Gardner's syndrome. The advantage of this approach is that it permits excision of excess skin over the cyst with esthetically pleasing hidden scars. The alternative to this procedure, a separate incision over each cyst, results in disfiguring and conspicuous scars.

Acute facial swelling can be life-threatening due to airway obstruction. Hemophiliac patients presenting with acute facial swelling must have accurate and expedient diagnosis. We report the case of acute nontraumatic swelling in a hemophiliac patient that was easily and accurately diagnosed by the use of computed tomography scan.

There is growing concern in academic emergency medicine as to the appropriateness of 24-hour faculty coverage in the teaching emergency department. We surveyed 170 teaching emergency departments, 49 of which had approved emergency medicine residencies, asking for information regarding 24-hour faculty coverage. We were able to separate each department into one of 15 profiles based on the two variables of average ED yearly census and hospital type. Seventy-three percent of university teaching hospital EDs and 65% of those with emergency medicine residencies have 24-hour faculty coverage; 83% of private teaching hospital EDs and 100% of those with emergency medicine residencies have 24-hour faculty coverage; and 79% of city/county teaching hospital EDs and 80% of those with emergency medicine residencies have 24-hour faculty coverage.