Treatment with stromal vascular fraction of Peyronie's disease - a study protocol.

INTRODUCTION: Peyronie´s disease is the result of an acquired fibrotic plaque in the tunica albuginea. It remains unknown why the condition appears, but it seems to affect up to 9% of all men. It can result in a debilitating curvature of the erect penis, which has extensive impact on the quality of life for many men. Thus, the disease may result in low self-esteem, depression and impaired sexual performance. METHODS: This is a prospective pilot study investigating the feasibility and safety of stromal vascular fraction injection into the plaque of 22 men with Peyronie´s disease in the chronic phase. The stromal vascular fraction is obtained from a small liposuction of 250 ml fat in general anaesthesia and injected the same day. CONCLUSION: We hope to show that injection of stromal vascular fraction is safe and effective in reducing curvature in men with Peyronie´s disease. FUNDING: The study was made possible with funding from: the Region of Southern Denmark, Louis-Hansen Fund, Lizzi and Mogens Staal Fund, Karola Jørgensen Fund, Marie and Børge Kroghs Fund, the Senior Doctors Research Fund OUH, the Fund for gentle Surgery OUH and the PhD fund of the executive board of the South West Denmark Hospital. The funding sources had no influence on the trial design, data collection, analysis or publication. CLINICALTRIALS: gov NCT04771442, EudraCT 2020-004297-22, Danish Medicines Agency 2020090057, National Ethics Committee 74705 and Danish Data Protection Agency (record no. 1/21757).

Preoperative intravenous iron treatment - a cohort study on colorectal cancer recurrence.

Background: Intravenous (i.v.) iron treatment has been speculated to increase the malignant potential of colorectal malignancies but also to enhance the immune systems potential to fight the invasive tumor. Clinical data however is very limited. We investigate if preoperative i.v. iron treatment is associated with colorectal cancer (CRC) recurrence. Methods: Retrospective cohort study on surgical CRC patients with iron deficiency anemia (1st March 2013 - 31st December 2019). Patients were grouped based on whether they had received preoperative treatment with i.v. iron. Local data was combined with data from the National Danish Health registries to identify recurrences, death, and emigration. Survival analysis, including Kaplan-Meyer curves and multivariate competing risk analysis adjusting for sex, age, ASA-group, tumor stage, surgical radicality, and miss match repair status was performed. Results: Of 1228 patients, 125 were available for analysis. 89 patients had received preoperative i.v. iron and 36 had not. The two groups were comparable on baseline and surgical characteristics. Median follow-up times were 4.74 in iron treated patients and 5 years in patients not receiving iron treatment. Five-year rate of non-recurrence was 85 % (0.74-0.91) in the i.v. iron treated group vs. 82 % (0.64-0.91) in the control group, non-significant difference. Multivariate survival analysis did not find iron treatment to be associated with recurrence rates (Hazard Ratio 0.88 (95 % ci; 0.31-2.51). Conclusion: No association between preoperative i.v. iron treatment and the five-year cancer recurrence rate in iron deficient anemic CRC patients was found.

Peyronie's disease questionnaire: translation into Danish and cultural adaptation.

Background: Peyronie's disease has an impact on men's mental and physical health. Aim: We sought to translate the Peyronie's Disease Questionnaire into Danish, adapt it to the Danish cultural setting, and test it in a Danish population. Methods: Translation of the Peyronie's Disease Questionnaire was performed according to the guidelines for adapting health status measures for use in languages other than the source language by Beaton et al. The validated American Peyronie's Disease Questionnaire was developed to monitor patient symptoms after an intervention and to inspire a subsequent dialogue about physical and psychological symptoms with a healthcare provider, thereby allowing the patient and the healthcare professional to choose the best treatment. The expert committee agreed on a Danish version after cross-cultural adaptation. The Danish Peyronie's Disease Questionnaire was sent by electronic mail to a preselected group of 41 men with Peyronie's disease. Outcomes: After completing the questionnaire, 32 men participated in a video interview regarding the questionnaire and were asked to identify any problematic fields or areas open to misunderstanding. Results: The Peyronie's Disease Questionnaire underwent major modifications in light of the comments of the first 10 respondents. Thereafter, only minor changes were made until data saturation was reached after 27 of the 32 respondents had been interviewed. In 87% of respondents Peyronie's disease bothered from the last time they had intercourse, and 93% of the men experienced being bothered by having intercourse less often. Peyronie's disease made 73% of respondents feel bodily discomfort, and 88% had intercourse less often than they used to have due to Peyronie's disease. Clinical Implications: The Peyronie's Disease Questionnaire is a valuable tool in the crucial task of addressing Peyronie's disease, providing insight into the mental and sexual health problems as well as physical challenges faced by patients. Strengths and Limitations: The interviewer's modest experience in conducting interviews is believed to have been duly compensated for by continuous and accumulating learning-while-doing process because the same interviewer conducted all of the interviews and did so consecutively. Conclusions: Danish men expressed satisfaction with the questionnaire and found it valuable as a tool when visiting the doctor for the first time.

Using fecal immunochemical test values below conventional cut-off to individualize colorectal cancer screening.

Background and study aims Of the participants in the Danish screening program, 89.9 % to 92.5 % have fecal immunochemical test (FIT) values < 10 µg/g feces (equivalent to 50 ng hemoglobin/mL buffer). This study aimed to investigate the risk of interval colorectal cancer (CRC) in this group before the next biennial screening round. Patients and methods This cohort study included all citizens from the region of Southern Denmark who participated in the Danish bowel screening program from 2014 trough 2016 and had a FIT value < 10 µg/g feces. Individuals receiving a CRC diagnosis were identified through the national CRC registry, with a follow up of 2 years corresponding to the current screening interval. We also examined the 3-year CRC incidence. Hazard ratios (HRs) were estimated using univariate and multivariate Cox proportional hazard regression models. Results Data from 185,654 citizens presenting with a FIT value < 10 µg/g feces were eligible for analysis. Overall, interval CRC incidence was 0.07 % within 2 years with HRs of 4.16 (95 % confidence interval [CI] 2.67;6.48) and 5.8 (95 % CI 3.34;10.05) for FIT values of 4 to 6.9 µg/g feces and 7 to 9.9 µg/g feces, respectively, compared to those having a FIT value below the limit of quantification of 4 µg/g feces. After 3 years, the overall CRC incidence increased to 0.14 %; however, this was not significant. Conclusions This study demonstrates a positive correlation between FIT value and risk of interval cancer even for very low values. It further suggests that an increase in the screening interval could be reasonable in the low FIT categories.

Preoperative Intravenous Iron Treatment in Colorectal Cancer: Experience From Clinical Practice.

INTRODUCTION: Anemia is associated with increased postoperative morbidity and mortality in abdominal surgery. In clinical trials, preoperative i.v. iron treatment increases the preoperative hemoglobin (Hb) concentration but the effect on transfusion rates are not consistent. This study reports on the experience with preoperative i.v. iron treatment in surgical colorectal cancer (CRC) patients in clinical practice. METHODS: A registry-based cohort study. Surgical colorectal cancer patients with iron deficiency anemia were compared after division into two groups; those who preoperatively received i.v. iron treatment and those who did not. Primary outcomes were preoperative changes in Hb and the difference in perioperative red blood cell transfusion (RBCT) rates. Postoperative complications and mortality rates were analyzed and a descriptive analysis on what triggered blood transfusions were performed. RESULTS: A total of 170 patients were included. Of these, 122 had received preoperative i.v. iron treatment and 48 had not. The perioperative transfusion rate was 45% (55/122) in the treatment group and 40% (19/48) in the control group (non-significant difference). The preoperative changes in Hb levels were not different between the two groups. Transfusion practice appeared more liberal and preceded by higher Hb levels that was guided by the National transfusion guideline. I.v. iron treated patients had a higher rate of postoperative complications. No differences were found on length of stay (LOS) or postoperative mortality. CONCLUSIONS: Preoperative i.v. iron treatment was neither associated with a rise in Hb concentrations at the time of surgery, nor with a reduction in the likelihood of receiving perioperative red blood cell transfusions (RBCT) in colorectal cancer (CRC) patients with iron deficiency anemia.

A rare case of a herniated acute appendicitis.

Acute appendicitis (AA) is the most common cause of acute abdomen worldwide and untreated it can lead to abscess formation, purulent or faeculent peritonitis, sepsis and death. This paper presents a rare case of an AA herniated in a retro-psoas muscle defect, which has not previously been reported in the literature. Our patient's diagnosis and management was delayed due to the unusual presentation. This case emphasizes the importance to utilize AA scoring algorithms to aid decision-making as they have shown to reduce admissions, optimize the use of diagnostic imaging and reduce negative surgical explorations.

Time-of-day variation in the diagnostic quality of screening colonoscopies: a registry-based study.

BACKGROUND: The diagnostic quality of screening colonoscopies has been found to differ between morning and afternoon. Specifically, the adenoma detection rate (ADR) is higher in the morning. Our aim was to assess if time-of-day dependent differences in colonoscopy quality exist in a Danish screening setting. Following national screening guidelines, an individual will be exempt from screening invitations for 8 years if the colonoscopy is without pathology. Therefore, it is of utmost importance to identify factors systematically affecting the detection of lesions. METHODS: This was a single-center study of screening colonoscopies performed between 2014 and 2018. Records were retrieved from the Danish Colorectal Cancer Screening Database and coupled with local data. The ADR and the cecal intubation rate were compared between morning (8-12 a.m.) and afternoon (12-4 p.m.) colonoscopies. Multivariate logistic regression analysis was performed. RESULTS: A total of 3659 screening colonoscopies were included. The ADR was 51% in the morning and 58% in the afternoon. Multivariate analysis found this statistically significant, with the "afternoon vs. morning" odds ratio for adenoma detection being 1.4 (95% confidence interval 1.17-1.68; P<0.001). The cecal intubation rate was 95.6% in the morning and 94.7%, a non-significant difference. CONCLUSIONS: The ADR of screening colonoscopies was higher in the afternoon. Our study highlights the need for local/regional evaluation of factors affecting colonoscopy quality to address such issues. A clean colonoscopy exempts the patient from subsequent screening invitations for 8 years. Therefore, any observed systematic differences in quality must be addressed and eliminated.

Colon capsule endoscopy in colorectal cancer screening: Interim analyses of randomized controlled trial CareForColon2015.

Background and study aims The Danish CareForColon2015 trial, launched in 2020 as part of the Danish Colorectal Cancer Screening program, is the largest randomized controlled trial to date on colon capsule endoscopy (CCE). This paper presents the interim analysis with the objective of ensuring the safety of patients in the intervention group and evaluating the clinical performance of the trial's predefined clinical parameters. Patients and methods We evaluated the initial 234 CCEs according to quality, safety, and completion. The participation rates and preference distribution of all individuals invited were analyzed and sample size calculations were adjusted. Results Fecal immunochemical test and diagnostic participation rates were 62.1 % and 91.1 %, respectively. The completion rate for CCEs was 67.9 % and the rate of conclusive investigations was 80.3 %. The polyp detection rate (PDR) was high (73.5 %), only two (0.85 %) technical failures in 234 videos were observed, and six suspected cancers were identified (2.6 %). No major adverse events were recorded. The required number of invitations had been underestimated due to inaccurate assumptions in sample size calculations. Conclusions The trial was efficient and safe in terms of CCE quality and time to diagnostic investigation. Participation rates and PDRs were high. The proportion of suspected cancers was lower than expected and will be followed. The completion rate for CCEs was acceptable but lower than expected and the CCE procedure was reviewed for potential improvements and Resolor was added to the regime. The number of invitations for the intervention group of the trial has been adjusted from 62,107 to 185,153.

Risk of post colonoscopy colorectal cancer following screening colonoscopy with low-risk or no adenomas: A population-based study.

AIM: In the Danish faecal occult blood test based bowel cancer screening programme, the first round was rolled out over 4 years. After roll-out, the planned faecal test recall procedure for individuals with either no or low risk adenomas at colonoscopy is 8 and 2 years, respectively. Here, we aimed to investigate the post colonoscopy colorectal cancer incidence in these two groups. METHODS: All Danish screening individuals from 2014 to 2015 with a positive faecal test and either no or low risk adenomas at colonoscopy were included and followed for 3 years post screening for the event of colorectal cancer through national registries. RESULTS: Out of 533,023 submitted faecal tests and 36,673 positive tests, 17,627 had no or low risk adenomas. We identified 60 (0.34%) individuals diagnosed with colorectal cancer within 3 years, 18 (0.29%) in the low risk adenoma group, and 42 (0.37%) in the no adenomas group (p = 0.44). Advancing age (HR = 1.079, p < 0.001) and higher faecal test value (HR = 1.001, p = 0.002) increased hazard of colorectal cancer occurrence, whereas male sex (HR = 1.3, p = 0.308) and having low risk adenomas (HR = 0.729, p = 0.264) did not. CONCLUSION: We found no difference in post colonoscopy colorectal cancer occurrence between individuals with either no or low risk adenomas. Instead, advancing age and increased faecal test value was associated with a higher risk of post colonoscopy colorectal cancer.

Feature Point Tracking-Based Localization of Colon Capsule Endoscope.

In large bowel investigations using endoscopic capsules and upon detection of significant findings, physicians require the location of those findings for a follow-up therapeutic colonoscopy. To cater to this need, we propose a model based on tracking feature points in consecutive frames of videos retrieved from colon capsule endoscopy investigations. By locally approximating the colon as a cylinder, we obtained both the displacement and the orientation of the capsule using geometrical assumptions and by setting priors on both physical properties of the intestine and the image sample frequency of the endoscopic capsule. Our proposed model tracks a colon capsule endoscope through the large intestine for different prior selections. A discussion on validating the findings in terms of intra and inter capsule and expert panel validation is provided. The performance of the model is evaluated based on the average difference in multiple reconstructed capsule's paths through the large intestine. The path difference averaged over all videos was as low as 4±0.7 cm, with min and max error corresponding to 1.2 and 6.0 cm, respectively. The inter comparison addresses frame classification for the rectum, descending and sigmoid, splenic flexure, transverse, hepatic, and ascending, with an average accuracy of 86%.

Iron deficiency in colorectal cancer patients: a cohort study on prevalence and associations.

AIM: The aim of this work was to estimate the prevalence of iron deficiency in patients diagnosed with colorectal cancer (CRC) and to clarify its association with patient- and tumour-related characteristics. METHOD: This was a single-centre registry-based cohort study. Iron status was routinely evaluated upon diagnosis of CRC, and these data were coupled with patient- and tumour-specific data from the Danish CRC Group Registry (2013-2018). Data were analysed using multivariate logistic regression. RESULTS: Out of 846 patients, 543 (64%) were iron deficient. There was an association between increasing depth of invasion and iron deficiency, with odds ratios (ORs) of iron deficiency being 2.8 (p = 0.001, CI 1.5-5.1), 4.22 (p < 0.001, CI 2.48-7.18) and 4.63 (p < 0.001, CI 2.30-9.34) for T-stages 2, 3 and 4, respectively. Right-sided tumours had an OR of 3.54 (p < 0.001, CI 2.22-5.67) of iron deficiency compared with left-sided tumours. Tumours diagnosed through the national CRC screening programme were less likely to be associated with iron deficiency (OR 0.34, CI 0.22-0.52), while female gender was associated with an increase in the odds for iron deficiency (OR 1.91, CI 1.33-2.76). Iron deficiency was prevalent in 88% of anaemic patients and 43% of nonanaemic patients. CONCLUSION: Iron deficiency was highly prevalent in patients diagnosed with CRC. Increased depth of tumour invasion, right-sided location and female gender were all associated with higher odds for iron deficiency, while patients diagnosed through the national screening programme were associated with lower odds for iron deficiency. A large proportion of patients with a normal haemoglobin were also iron deficient.

Screening individuals' experiences of colonoscopy and colon capsule endoscopy; a mixed methods study.

BACKGROUND: The standard investigation in colorectal cancer screening (optical colonoscopy [OC]) has a less invasive alternative with the colon capsule endoscopy (CCE). The experiences of screening individuals are needed to support a decision aid (DA) and to provide a patient view in future health technology assessments (HTA). We aimed to explore the experiences of CCE at home and OC in an outpatient clinic by screening participants who experienced both investigations on the same bowel preparation. METHODS: In a mixed methods study, Danish screening individuals with a positive immunological fecal occult blood test (FIT) were consecutively included and underwent both CCE and OC in the same bowel preparation. They answered questionnaires about discomfort during CCE, delivered at home, and during a following OC in the outpatient clinic. Data were calculated in percentages and Wilcoxon signed rank test was used for comparisons. Among the 253 included patients, 10 participants were selected for a semi-structured interview about their experiences of the two examinations. The analysis and interpretation of the transcribed data were inspired by Ricoeur. RESULTS: Questionnaire data were received from 239 participants and revealed significant less discomfort during the CCE than the OC. Interview data included explained discomfort elements in two categories: 'The examination' and 'The setting'. Compared to OC, the CCE was experienced with less pain, embarrassment and invasiveness, but presented challenges and disadvantages as well, i.e., a large camera capsule to swallow, a longer waiting time for test results after CCE and an additional OC, if pathologies were found. The home setting for CCE delivery made the participants feel less like they were ill or patients less restricted and that they received more personal care, but could induce technical challenges. CONCLUSION: In screening individuals, CCE at home was associated with significantly less discomfort compared to OC at a hospital, and multiple reasons for this was identified.

[The effect of primary colonoscopy versus follow-up colonoscopy in screening for colorectal cancer].

Balancing indications for primary and follow-up colonoscopy in screening is important. In the lowest faecal test positive range of 100-150 ng/ml the rate of cancer is 1.9%, and the rate of intermediate and high-risk adenomas is 16.7%. International studies suggest, that only selected groups have comparable rates of significant findings at follow-up, and the risk normalises after one colonoscopy. In this review it is found, that in the current Danish screening programme for colon cancer the indications of primary screening and follow-up colonoscopy seem to be off-balance, but no national data exist on follow-up.

Intra and inter-observer agreement on polyp detection in colon capsule endoscopy evaluations.

BACKGROUND: Colon capsule endoscopy is a promising technique for evaluation of the colon, but its reproducibility is still unknown. OBJECTIVE: This study assesses intra and inter-observer agreement in evaluations of colon capsule endoscopy videos. METHODS: Forty-two complete colon capsule endoscopy investigations were analysed by three experts and two beginners. Intra-observer agreement was assessed in paired readings of two experts and two beginners. Agreement was determined by the intraclass correlation coefficient: poor (<0.5), moderate (0.5-0.75), good (0.75-0.9) and excellent (>0.9). RESULTS: Agreement on 'indication for a following colonoscopy' based on the number and size of detected polyps and bowel cleansing quality was poor among all observers. Agreement among experts on the detection of large polyps and number of polyps was moderate, but agreement on bowel cleansing quality was poor. Beginners were in moderate agreement with the experts on polyp detection. Intra-observer agreement in experts was moderate to excellent for the detection of large polyps (≥10 mm), excellent for the number of polyps, and poor to moderate for bowel cleansing quality. Intra-observer agreement in beginners was poor to moderate for all variables. CONCLUSIONS: This study shows a poor agreement on 'indication for a following colonoscopy', but a high intra and inter-observer agreement for polyp detection among experts, as well as a moderate agreement between beginners and experts.Trial registration: NCT02303756.

Booster medication to achieve capsule excretion in colon capsule endoscopy: a randomized controlled trial of three regimens.

Background and study aims To achieve a complete colon capsule endoscopy, the entire colon must be visualized, clean and filled with clear fluids. The primary aim was to compare three booster regimens in colon capsule endoscopy in achieving capsule excretion within recording time. Secondary aims were quality of bowel cleansing and completion rate (both adequate cleansing and capsule excretion). Patients and methods Patients scheduled for follow-up colonoscopy due to previous neoplastic findings or familial history of colorectal cancer aged 18 to 70 years were eligible. Bowel preparation was 2-L split doses of polyethylene glycol. Patients were randomized to three booster regimens of either polyethylene glycol (Group A), sulfate-based solution (Group B) or polyethylene glycol with iodine oral contrast (Group C). Results One hundred eighty participants were included and randomized into three groups of 60. Capsule excretion was 70 % (95 % CI: 58 - 80) in Group A, 73 % (95 % CI: 61 - 83) in Group B and in 68 % (95 % CI: 56 - 79) in Group C, no statistically significant differences. Bowel cleansing grade was statistically significant better in Group B compared to Group A ( P  = 0.03), but there were no statistically significant differences between Groups C and A ( P  = 0.40). Complete examination rate was 65 % (95 % CI: 53 - 77), 72 % (95 % CI: 61 - 83) and 62 % (95 % CI: 50 - 74) in Group A, B and C respectively, not statistically significant different. Conclusions Sulfate-based solution resulted in statistically significant better bowel cleansing compared to polyethylene glycol. Overall the excretion and completion rate was suboptimal. Achieving a high completion rate using patient-tolerable and low-risk compounds is still a challenge.

Assessment of bowel cleansing quality in colon capsule endoscopy using machine learning: a pilot study.

BACKGROUND AND STUDY AIMS: The aim of this study was to develop a machine learning-based model to classify bowel cleansing quality and to test this model in comparison to a pixel analysis model and assessments by four colon capsule endoscopy (CCE) readers. METHODS: A pixel analysis and a machine learning-based model with four cleanliness classes (unacceptable, poor, fair and good) were developed to classify CCE videos. Cleansing assessments by four CCE readers in 41 videos from a previous study were compared to the results both models yielded in this pilot study. RESULTS: The machine learning-based model classified 47 % of the videos in agreement with the averaged classification by CCE readers, as compared to 32 % by the pixel analysis model. A difference of more than one class was detected in 12 % of the videos by the machine learning-based model and in 32 % by the pixel analysis model, as the latter tended to overestimate cleansing quality. A specific analysis of unacceptable videos found that the pixel analysis model classified almost all of them as fair or good, whereas the machine learning-based model identified five out of 11 videos in agreement with at least one CCE reader as unacceptable. CONCLUSIONS: The machine learning-based model was superior to the pixel analysis in classifying bowel cleansing quality, due to a higher sensitivity to unacceptable and poor cleansing quality. The machine learning-based model can be further improved by coming to a consensus on how to classify cleanliness of a complete CCE video, by means of an expert panel.

Left ventricular longitudinal strain for perioperative cardiac monitoring in aortic aneurysm surgery using transthoracic 2-dimensional echocardiography: a feasibility and repeatability study.

OBJECTIVE: This study investigated perioperative echocardiographic image quality, the feasibility, and intra- and interobserver repeatability of left ventricular longitudinal two-dimensional strain echocardiography (2DSE) in aortic aneurysm surgery. DESIGN: A prospective, descriptive method evaluation. SETTING: A single-center study. PARTICIPANTS: Eighteen patients undergoing elective open infrarenal aortic aneurysm repair. INTERVENTION: No intervention was made. MEASUREMENTS AND MAIN RESULTS: Four echocardiographic examinations were made: E1, preoperatively; E2, within 4 hours after surgery; E3, the first postoperative day; and E4, the second postoperative day. Four-chamber, 2-chamber, and longitudinal axis apical views were achieved. Image quality was scored visually on a scale from 1 to 5 with 5 as the best, and the 2-dimensional strain echocardiography (2DSE) software was applied to measure peak systolic strain. Blinded analyses were performed twice by 1 observer and once by a second observer. Image quality decreased significantly after surgery as compared with the preoperative examination, but 72% of patients had at least 1 image scoring >/=3 through all examinations. The software was able to measure the segmental and global left ventricular peak systolic strain in 80% and 61%, respectively, for the first observer and 71% and 26%, respectively, for the second observer. The coefficients of repeatability for intra- and interobserver measurements were 5.5% and 7.3% for segmental strain and 1.6% and 3.5% for global strain. 2DSE was more feasible and repeatable when echocardiographic images were good. CONCLUSION: Feasibility and repeatability of 2DSE is good but affected by image quality. This study shows that 2DSE can be used in a clinical setting.