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Background: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup., Methods: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722)., Results: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6)., Conclusions: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate All participants provided informed consent and the study was approved by the Danish Committees on Health Research Ethics (j. no 1-10-72-223-14, H-4-2013-050, and 1-10-72-3-18) and reported according to STROBE guidelines [36]., (© 2024. The Author(s).)

Introduction: Circulating tumor (ctDNA) can be used to detect residual disease after cancer treatment. Detecting low-level ctDNA is challenging, due to the limited number of recoverable ctDNA fragments at any target loci. In response, we applied tumor-informed whole-genome sequencing (WGS), leveraging thousands of mutations for ctDNA detection., Methods: Performance was evaluated in serial plasma samples (n = 1283) from 144 stage III colorectal cancer patients. Tumor/normal WGS was used to establish a patient-specific mutational fingerprint, which was searched for in 20x WGS plasma profiles. For reproducibility, paired aliquots of 172 plasma samples were analyzed in two independent laboratories. De novo variant calling was performed for serial plasma samples with a ctDNA level > 10 % (n = 17) to explore genomic evolution., Results: WGS-based ctDNA detection was prognostic of recurrence: post-operation (Hazard ratio [HR] 6.75, 95 %CI 3.18-14.3, p < 0.001), post-adjuvant chemotherapy (HR 28.9, 95 %CI 10.1-82.8; p < 0.001), and during surveillance (HR 22.8, 95 %CI 13.7-37.9, p < 0.0001). The 3-year cumulative incidence of ctDNA detection in recurrence patients was 95 %. ctDNA was detected a median of 8.7 months before radiological recurrence. The independently analyzed plasma aliquots showed excellent agreement (Cohens Kappa=0.9, r = 0.99). Genomic characterization of serial plasma revealed significant evolution in mutations and copy number alterations, and the timing of mutational processes, such as 5-fluorouracil-induced mutations., Conclusion: Our study supports the use of WGS for sensitive ctDNA detection and demonstrates that post-treatment ctDNA detection is highly prognostic of recurrence. Furthermore, plasma WGS can identify genomic differences distinguishing the primary tumor and relapsing metastasis, and monitor treatment-induced genomic changes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. CLA reports collaborations with C2i Genomics and Natera. AZ, BO, RV, TL, and DM report stock options at C2i Genomics. AZ is the co-founder and a member of the board of directors of C2i Genomics. BO is the co-founder and CTO of C2i Genomics. SG, MK, JL, DG, RP, JS, DA, TL, YC, ZD, IT, and UA are employees of C2i Genomics. The opinions, results, and conclusions reported in this article are those of the authors and are independent of any competing interests. LD has sponsored research agreements with C2i Genomics, Natera, AstraZeneca, Photocure, and Ferring and has an advisory/consulting role at Ferring, MSD and UroGen. LD has received speaker honoraria from AstraZeneca, Pfizer and Roche and received travel support from MSD. LD is a board member at BioXpedia., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment. Digital PCR (dPCR) offers low analysis costs and turnaround times of less than a day, making it ripe for clinical implementation. Here, we used tumor-informed dPCR for ctDNA detection in a large colorectal cancer (CRC) cohort to evaluate the potential for post-operative risk assessment and serial monitoring, and how the metastatic site may impact ctDNA detection. Additionally, we assessed how altering the ctDNA-calling algorithm could customize performance for different clinical settings., Patients and Methods: Stage II-III CRC patients (N = 851) treated with a curative intent were recruited. Based on whole-exome sequencing on matched tumor and germline DNA, a mutational target was selected for dPCR analysis. Plasma samples (8 ml) were collected within 60 days after operation and-for a patient subset (n = 246)-every 3-4 months for up to 36 months. Single-target dPCR was used for ctDNA detection., Results: Both post-operative and serial ctDNA detection were prognostic of recurrence [hazard ratio (HR) = 11.3, 95% confidence interval (CI) 7.8-16.4, P < 0.001; HR = 30.7, 95% CI 20.2-46.7, P < 0.001], with a cumulative ctDNA detection rate of 87% at the end of sample collection in recurrence patients. The ctDNA growth rate was prognostic of survival (HR = 2.6, 95% CI 1.5-4.4, P = 0.001). In recurrence patients, post-operative ctDNA detection was challenging for lung metastases (4/21 detected) and peritoneal metastases (2/10 detected). By modifying the cut-off for calling a sample ctDNA positive, we were able to adjust the sensitivity and specificity of our test for different clinical contexts., Conclusions: The presented results from 851 stage II-III CRC patients demonstrate that our personalized dPCR approach effectively detects MRD after operation and shows promise for serial ctDNA detection for recurrence surveillance. The ability to adjust sensitivity and specificity shows exciting potential to customize the ctDNA caller for specific clinical settings., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this work, we evaluated the feasibility of Raman spectroscopy as an in-line raw material characterization tool for industrial process control of the hydrolysis of poultry rest raw material. We established calibrations (N = 59) for fat, protein, ash (proxy for bone) and hydroxyproline (proxy for collagen) in ground poultry rest raw material. Calibrations were established in the laboratory using poultry samples with high compositional variation. Samples were measured using a wide area illumination Raman probe at varying working distance (6 cm, 9 cm, 12 cm) and probe tilt angle (0°, 30°) to mimic expected in-line variations in the measurement situation. These moderate variations did not significantly affect performance for any analytes. The obtained calibrations were tested in-line with continuous measurements of the ground poultry by-product stream at a commercial hydrolysis facility over the course of two days. Measurements were acquired under demanding conditions, e.g. large variations in working distance. Reasonable estimates of compositional trends were obtained. Validation samples (N = 19) were also reasonably well predicted, with RMSEP corr  = [0.14, 1.37, 2.36, 1.51]% for hydroxyproline, protein, fat and ash, respectively. However, there were indications that further calibration development and robustification of pre-processing would be advantageous, particularly with respect to hydroxyproline and protein models. It is the authors' impression that with such efforts, potentially in combination with development of practical measurement setup, the use of Raman spectroscopy as a process control tool for the hydrolysis of poultry rest raw materials is within reach., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tiril Aurora Lintvedt reports equipment, drugs, or supplies was provided by MarqMetrix Inc., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Follow-up after an episode of colonic diverticulitis is a common indication for colonoscopy, even though studies have shown a low risk of positive findings in this population. Our objective is to investigate colon capsule endoscopy (CCE) as a follow-up examination in patients with colonic diverticulitis compared with colonoscopy, particularly regarding patient satisfaction and clinical performance., Methods and Analysis: We will conduct a single-centre prospective randomised controlled trial. Patients seen at Odense University Hospital with acute diverticulitis confirmed by CT will be included and randomised to either follow-up by colonoscopy or CCE. Detection of suspected cancer, more than two polyps or any number of polyps larger than 9 mm in CCE will generate an invitation to a diagnostic colonoscopy for biopsies or polyp removal. We will compare colonoscopy and CCE regarding patient satisfaction and tolerance, the number of complete examinations, the number of patients referred to a subsequent colonoscopy after CCE and the prevalence of diverticula, polyps, cancers and other abnormal findings., Ethics and Dissemination: Informed consent will be obtained from all participants before randomisation. The study was approved by the regional ethics committee (ref. S-20210127) and the Danish Data Protection Agency (ref. 22/43235). After completion of the trial, we plan to publish two articles in high-impact journals. One article on both primary and secondary outcomes., Trial Registration Number: NCT05700981., Competing Interests: Competing interests: TB-M has received grants from the Region of Southern Denmark and the Centre of Clinical Implementation for Capsule Endoscopy (CICA). TB-M is member of an Advisory Board for Medtronic regarding optimising bowel preparation in colon capsule endoscopy. Anastasios Koulaouzidis is codirector and shareholder of iCERV Ltd. He has received consultancy fees and travel support from Jinshan Ltd, Diagmed Healthcare Ltd and research support (grant) from ESGE/Given Imaging Ltd and IntroMedic/SynMed, honoraria from Jinshan and Medtronic and has participated in advisory board meetings hosted by ANKON., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is a potential benefit on long-term outcomes following complete mesocolic excision (CME) for right-sided colon cancer when compared to conventional colectomy. This study aims to analyze the learning curve and short-term outcomes of laparoscopic CME with intracorporeal anastomosis (ICA) for right-sided colon cancer in the hands of experienced colorectal surgeons., Methods: A two-center cohort study of consecutive patients undergoing right-sided colectomy from September 2021 to May 2022 at two tertiary colorectal centers in Denmark. Learning curves of surgical time were estimated using a cumulative sum analysis (CUSUM)., Results: A total of 61 patients were included. According to the CUSUM analysis, 32 cases were needed to obtain a peak in operative time, resulting in a decrease in time consumption (group 1/learning phase: 217.2 min [SD 53.6] and group 2/plateau phase 191.6 min [SD 45.1], p = 0.05). There was a nonsignificant reduction in the rates of severe surgical complications (Clavien-Dindo > 3) (13% vs. 7%, p = 0.67) between the two groups, while the length of hospital stay remained constant (median 3.0 days, interquartile range, IQR [2.0; 4.0])., Conclusion: The learning curve of laparoscopic CME with ICA for right-sided colon cancer demonstrated that 32 cases were needed to obtain a plateau phase expressed by operative time., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL., Method: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion., Results: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04)., Conclusion: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups., Trial Registration: ClinicalTrials.gov Identifier: NCT04766060., (© 2023. The Author(s).)

Background: Colon capsule endoscopy (CCE) was introduced in our department on two indications; following incomplete colonoscopy as an alternative to CT colonography, and in patients with a history of incomplete colonoscopy as an alternative to anesthesia-assisted (AA) colonoscopy. We aimed to compare the quality of CCE, defined by completion rate and polyp detection rate (PDR), with that of CT colonography and AA colonoscopy, respectively., Methods: Patients referred for CCE from May 2020 until November 2021 were consecutively included in this prospective cohort study. Demographics, indication and CCE outcomes were registered from the electronic patient record. Completion rate and PDR in CCE as an alternative to CT colonography were compared with those of a historical cohort undergoing CT colonography following incomplete colonoscopy. Completion rate and PDR in CCE as an alternative to AA colonoscopy were compared with those of a time true parallel cohort undergoing AA colonoscopy., Results: In 65 patients undergoing CCE, 36 (57%) were referred as an alternative to CT colonography. The completion rate in this group was 44% compared to 96% in CT colonography (p < 0.001). The PDR in complete CCE in this group was 75% in CCE compared to 20% in CT colonography (p < 0.001). The remaining 27 (43%) of the sample were referred for CCE as an alternative to AA colonoscopy. The completion rate in this group was 33% compared to 100% in AA colonoscopy (p < 0.001). The PDR in complete CCE in this group was 78% in CCE compared to 35% in AA colonoscopy (p = 0.013)., Conclusions: The completion rate of CCE following incomplete colonoscopy is inferior to that of CT colonography and AA colonoscopy. The PDR of CCE was high, indicating an acceptable sensitivity in complete investigations, but in our settings the completion rate of CCE on this indication is unacceptably low., Clinical Trial Registration: NCT04307901 (ClinicalTrials.gov, March 13, 2020)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Raman spectroscopy was compared with near infrared (NIR) hyperspectral imaging for determination of fat composition (%EPA + DHA) in salmon fillets at short exposure times. Fillets were measured in movement for both methods. Salmon were acquired from several different farming locations in Norway with different feeding regimes, representing a realistic variation of salmon in the market. For Raman, we investigated three manual scanning strategies; i) line scan of loin, ii) line scan of belly and iii) sinusoidal scan of belly at exposure times of 2s and 4s. NIR images were acquired while the fillets moved on a conveyor belt at 40 cm/s, which corresponds to an acquisition time of 1s for a 40 cm long fillet. For NIR images, three different regions of interest (ROI) were investigated including the i) whole fillet, ii) belly segment, and iii) loin segment. For both Raman and NIR measurements, we investigated an untrimmed and trimmed version of the fillets, both relevant for industrial in-line evaluation. For the trimmed fillets, a fat rich deposition layer in the belly was removed. The %EPA + DHA models were validated by cross validation (N = 51) and using an independent test set (N = 20) which was acquired in a different season. Both Raman and NIR showed promising results and high performances in the cross validation, with R2 CV  = 0.96 for Raman at 2s exposure and R2 CV  = 0.97 for NIR. High performances were obtained also for the test set, but while Raman had low and stable biases for the test set, the biases were high and varied for the NIR measurements. Analysis of variance on the squared test set residuals showed that performance for Raman measurements were significantly higher than NIR at 1% significance level (p = 0.000013) when slope-and-bias errors were not corrected, but not significant when residuals were slope-and-bias corrected (p = 0.28). This indicated that NIR was more sensitive to matrix effects. For Raman, signal-to-noise ratio was the main limitation and there were indications that Raman was close to a critical sample exposure time at the 2s signal accumulation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tiril Aurora Lintvedt reports equipment, drugs, or supplies was provided by MarqMetrix Inc., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients., Methods: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients., Results: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12-2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22-5.03) and Stage II (OR = 1.76, 95%CI: 1.11-2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44-1.53) patients., Conclusion: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.

Scandinavian Surgical Society (SSS), Nordisk Kirurgisk Förening, founded in 1893, is the oldest international surgical society in the world. The purpose of the society is to promote scientific and clinical work as well as education in the field of surgery in the Nordic countries; Denmark, Finland, Sweden, Norway and Iceland. Nordic co-operation has long traditions in the medical field. The surgical development through the surgical communities and the long-term co-operation between the Nordic surgeons have affected the patient care and development of surgery throughout the Nordic region. An overview and a historical glance of the surgical communities in the Nordic countries from the 18th century are described as well as activities in the SSS from the beginning of 1893 to these days., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Raman spectroscopy is a viable tool within process analytical technologies due to recent technological advances. In this article, we evaluate the feasibility of Raman spectroscopy for in-line applications in the food industry by estimating the concentration of the fatty acids EPA + DHA in ground salmon samples (n = 63) and residual bone concentration in samples of mechanically recovered ground chicken (n = 66). The samples were measured under industry like conditions: They moved on a conveyor belt through a dark cabinet where they were scanned with a wide area illumination standoff Raman probe. Such a setup should be able to handle relevant industrial conveyor belt speeds, and it was studied how different speeds (i.e., exposure times) influenced the signal-to-noise ratio (SNR) of the Raman spectra as well as the corresponding model performance. For all samples we applied speeds that resulted in 1 s, 2 s, 4 s, and 10 s exposure times. Samples were scanned in both heterogenous and homogenous state. The slowest speed (10 s exposure) yielded prediction errors (RMSECV) of 0.41%EPA + DHA and 0.59% ash for the salmon and chicken data sets, respectively. The more in-line relevant exposure time of 1 s resulted in increased RMSECV values, 0.84% EPA + DHA and 0.84% ash, respectively. The increase in prediction error correlated closely with the decrease in SNR. Further improvements of model performance were possible through different noise reduction strategies. Model performance for homogenous and heterogenous samples was similar, suggesting that the presented Raman scanning approach has the potential to work well also on intact heterogenous foods. The estimation errors obtained at these high speeds are likely acceptable for industrial use, but successful strategies to increase SNR will be key for widespread in-line use in the food industry.

The aim of the present study was to critically evaluate the potential of using NIR and Raman spectroscopy for prediction of fatty acid features and single fatty acids in salmon muscle. The study was based on 618 homogenized salmon muscle samples acquired from Atlantic salmon representing a one year-class nucleus, fed the same high fish oil feed. NIR and Raman spectra were used to make regression models for fatty acid features and single fatty acids measured by gas chromatography. The predictive performance of both NIR and Raman was good for most fatty acids, with R 2 above 0.6. Overall, Raman performed marginally better than NIR, and since the Raman models generally required fewer components than respective NIR models to reach high and optimal performance, Raman is likely more robust for measuring fatty acids compared to NIR. The fatty acids of the salmon samples co-varied to a large extent, a feature that was exacerbated by the overlapping peaks in NIR and Raman spectra. Thus, the fatty acid related variation of the spectroscopic data of the present study can be explained by only a few independent principal components. For the Raman spectra, this variation was dominated by functional groups originating from long-chain polyunsaturated FAs like EPA and DHA. By exploring the independent EPA and DHA Raman models, spectral signatures similar to the respective pure fatty acids could be seen. This proves the potential of Raman spectroscopy for single fatty acid prediction in muscle tissue.

Background: Recent novel surgical techniques for resection of low rectal cancer have been introduced and these approaches have the potential to overcome anatomical limitations like obesity, narrow male pelvis and bulky and low tumours. Two of these procedures are robotic low anterior resection (RLAR) and transanal total mesorectal excision (TaTME).Both approaches have distinct advantages and limitations. There has been no head to head trial comparing RLAR and TaTME for patients with mid to low rectal cancer undergoing surgery by experienced surgeons. Previous studies looking at the oncological outcomes of either TaTME or robotic TME included many centres where the surgeons were on a learning curve and hence the true oncological outcomes and clinical benefits can not be measured accurately., Method: The inclusion criteria include experienced surgeons defined as minimum of 60 prior procedures with RLAR or TaTME. Successful oncological and clinical outcomes are defined as circumferential resection margin (CRM) ≥1 mm with limited postoperative morbidity (absence of Clavien-Dindo grade III-IV complications within 30 days after surgery). Local and distal recurrence rates with DFS over 3 years will be measured as primary outcome.Data will be collected prospectively and entered in a dedicated database., Discussion: The primary objective of this study is to conduct a multicentre prospective trial to investigate clinical outcomes, in particular disease free survival (DFS) in patients undergoing RLAR and TaTME. The additional goal is to investigate other efficacy measures, complications rates, health economic aspects and patient reported health related quality of life.This paper describes an important trial conducted in expert centres to establish the needed knowledge for a detailed comparison of outcomes for TaTME versus RLAR.This trial is the first comparative study, comparing TaTME and RLAR, seeking to establish foothold for tailor-made surgical treatment of low rectal cancer patients., Trial Registration: The trial is registered in clinicaltrials.gov September 2019. Clinicaltrials.gov id: NCT04200027., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Purpose: Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates., Experimental Design: We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples ( n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing., Results: Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7-13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4-167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9-172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1-6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography., Conclusions: Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making. See related commentary by Morris and George, p. 438 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Raman spectroscopy (RS) has for decades been considered a promising tool for food analysis, but widespread adoption has been held back by, e.g., high instrument costs and sampling limitations regarding heterogeneous samples. The aim of the present study was to use wide area RS in conjunction with surface scanning to overcome the obstacle of heterogeneity. Four different food matrices were scanned (intact and homogenized pork and by-products from salmon and poultry processing) and the bulk chemical parameters such as fat and protein content were estimated using partial least squares regression (PLSR). The performance of PLSR models from RS was compared with near-infrared spectroscopy (NIRS). Good to excellent results were obtained with PLSR models from RS for estimation of fat content in all food matrices (coefficient of determination for cross-validation (R 2 CV ) from 0.73 to 0.96 and root mean square error of cross-validation (RMSECV) from 0.43% to 2.06%). Poor to very good PLSR models were obtained for estimation of protein content in salmon and poultry by-product using RS (R 2 CV from 0.56 to 0.92 and RMSECV from 0.85% to 0.94%). The performance of RS was similar to NIRS for all analyses. This work demonstrates the applicability of RS to analyze bulk composition in heterogeneous food matrices and paves way for future applications of RS in routine food analyses.

In this case report, a tumour was found in the coecum under a colonoscopy, performed after positive screening test for colorectal cancer in an asymptomatic 61-year-old man. Pathology from biopsies showed numerous trophozoites in the lamina propria, compatible with Entamoeba histolytica. In faecal samples, E. histolytica was detected by species-specific real-time polymerase chain reaction. Infection caused by E. histolytica can occur several years after exposure. If E. histolytica is detected, treatment is always recommended as prevention for later development of invasive infection.

Dry matter (DM) content is one of the most important quality features of potatoes. It defines the physical properties of the potatoes and determines what kind of product the potatoes can be used for. This paper presents the results obtained by a novel prototype NIR (near-infrared) instrument designed to measure DM content in single potatoes in process. The instrument is based on interaction measurements to measure deeper into the potatoes. It measures rapidly, up to 50 measurements per second, allowing several moving potatoes to be measured per second. The instrument also enables several interactance distances to be recorded for each measurement. The instrument was calibrated based on three different potato varieties and the calibration measurements were done in a process plant, making the calibration model suitable for in-line use. A good calibration for DM was obtained by partial least squares regression ( RMSECV = 0.78% DM, R 2 = 0.91). The instrument was tested in-line in the process plant and several batches of potatoes were monitored for the estimation of the DM distribution per batch. Accuracy of DM determination as function of measurement position on the potato was studied, and results indicate that NIR scans along the center part of the potatoes give slightly better results compared to scans taken on either side of the center. Small differences in optical measurement geometry influence the accuracy of the calibration models, underlining the importance of optimizing instrument design for successful measurements.

The main purpose of this study was to investigate if Raman spectra recorded at the exact same position as drip loss measurements could improve prediction of drip loss in pork. One ventral and one dorsal cylindrical plug, cut from a standardized slice from Longissimus lumborum, were used to determine drip loss by EZ-DripLoss method and to collect Raman spectra, while ultimate pH was measured at another location. Partial least squares regression models were developed using spectra from each plug individually or averaged spectra from both plugs. The best models used spectra from the ventral plug, resulting in r cv 2 =0.75, root mean square error of cross-validation (RMSECV) = 1.27% and ratio of prediction to deviation (RPD) =2.0 for EZ-DripLoss and r cv 2 =0.72, RMSECV = 0.05 and RPD = 2.0 for ultimate pH. Results indicate that Raman spectroscopy can be used for rough screening of drip loss and pH in pork, and that the location chosen for collection of spectra can be very important for successful predictions., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Spectroscopic techniques can provide valuable information about post-mortem meat quality. In the current study, Raman, NIR and fluorescence spectroscopy was used to analyze pH, drip loss and intramuscular fat in pork longissimus lumborum (n = 122) at 4-5 days post-mortem. Results were promising for partial least squares regression (PLSR) from Raman spectroscopy, giving coefficients of determination from cross validation (r cv 2 ) ranging from 0.49 to 0.73 for all attributes examined. Important regions in the PLSR models from Raman spectroscopy were attributed to changes in concentrations of post-mortem metabolites and modifications of protein secondary structure. Near infrared and fluorescence spectroscopy showed limited ability to analyze quality, with r cv 2 ranging from 0.06 to 0.57 and 0.04 to 0.18, respectively. This study encourages further research on the subject of Raman spectroscopy as a technique for meat quality analysis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Degree of post-mortem proteolysis influences overall meat quality (e.g. tenderness and water holding capacity). Degradation of isolated pork myofibril proteins by μ-Calpain for 0, 15 or 45 min was analyzed using four spectroscopic techniques; Raman, Fourier transform infrared (FT-IR), near infrared (NIR) and fluorescence spectroscopy. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was used to determine degree of proteolysis. The main changes detected by FT-IR and Raman spectroscopy were degradation of protein backbones manifested in the spectra as an increase in terminal carboxylic acid vibrations, a decrease in CN vibration, as well as an increase in skeletal vibrations. A reduction in β-sheet secondary structures was also detected, while α-helix secondary structure seemed to stay relatively unchanged. NIR and fluorescence were not suited to analyze degree of proteolysis in this model system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to assess the potential clinical value of contrast enhanced laparoscopic ultrasonography (CE-LUS) as a screening modality for liver metastases during robotic assisted surgery for primary colorectal cancer (CRC)., Method: A prospective, descriptive (feasibility) study including 50 consecutive patients scheduled for robotic assisted surgery for primary CRC. CE-LUS was performed by 2 experienced specialists. Only patients without metastatic disease were included. Follow-up was obtained with contrast-enhanced CT imaging at 3 and 12 months postoperatively., Results: Fifty patients were included; 45 patients were available for final analysis. The patients were equally distributed between stage I, II, and III according to the TNM classification system. No liver metastasis was detected during LUS and CE-LUS. CE-LUS was easy to perform and there was no complication. Follow-up revealed no liver metastasis in any of the patients., Conclusion: CE-LUS did not increase the detection rate of occult liver metastasis during robotic assisted primary CRC surgery. The use of CE-LUS as a screening modality for detection of liver metastasis cannot be recommended based on this study, but larger controlled studies on high-risk patients seem relevant., (© 2017 Wiley Periodicals, Inc.)

Muscle cells undergo changes post-mortem during the process of converting muscle into meat, and this complex process is far from revealed. Recent reports have suggested programmed cell death (apoptosis) to be important in the very early period of converting muscle into meat. The dynamic balance that occurs between anti-apoptotic members, such as Bcl-2, and pro-apoptotic members (Bid, Bim) helps determine whether the cell initiates apoptosis. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to investigate if apoptosis is induced when oxygen is removed from the growth medium. Primary bovine muscle cells were differentiated to form myotubes, and anoxia was induced for 6h. The anoxic conditions significantly increased (P<0.05) the relative gene expression of anti- and pro-apoptotic markers (Aif, Bcl-2, Bid and Bim), and the PARK7 (P<0.05) and Grp75 (Hsp70) protein expressions were transiently increased. The anoxic conditions also led to a loss of mitochondrial membrane potential, which is an early apoptotic event, as well as cytochrome c release from the mitochondria. Finally, reorganization and degradation of cytoskeletal filaments occurred. These results suggest that muscle cells enters apoptosis via the intrinsic pathway rapidly when available oxygen in the muscle diminishes post-mortem.

The decline of pH and ultimate pH in meat postmortem greatly influences meat quality (e.g. water holding capacity). Four spectroscopic techniques, Raman, Fourier transform infrared (FT-IR), near infrared (NIR) and fluorescence spectroscopy, were used to study protein and amino acid modifications to determine pH-related changes in pork myofibril extracts at three different pH-levels, 5.3, 5.8 and 6.3. Protonation of side-chain carboxylic acids of aspartic and glutamic acid and changes in secondary structure, mainly the amide I-III peaks, were the most important features identified by Raman and FT-IR spectroscopy linked to changes in pH. Fluorescence spectroscopy identified tryptophan interaction with the molecular environment as the most important contributor to changes in the spectra. NIR spectroscopy gave no significant contributions to interpreting protein structure related to pH. Results from our study are useful for interpreting spectroscopic data from meat where pH is an important variable., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Primary muscle cell model systems from farm animals are widely used to acquire knowledge about muscle development, muscle pathologies, overweight issues and tissue regeneration. The morphological properties of a bovine primary muscle cell model system, in addition to cell proliferation and differentiation features, were characterized using immunocytochemistry, western blotting and real-time PCR. We observed a reorganization of the Golgi complex in differentiated cells. The Golgi complex transformed to a highly fragmented network of small stacks of cisternae positioned throughout the myotubes as well as around the nucleus. Different extracellular matrix (ECM) components were used as surface coatings in order to improve cell culture conditions. Our experiments demonstrated improved proliferation and early differentiation for cells grown on surface coatings containing a mixture of both glycosaminoglycans (GAGs) and fibrous proteins. We suggest that GAGs and fibrous proteins mixed together into a composite biomaterial can mimic a natural ECM, and this could improve myogenesis for in vitro cell cultures., (© 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Purpose: To identify the key parameters involved in cereal starch digestion and associated glycaemic response by the utilisation of a dynamic gastro-duodenal digestion model., Methods: Potential plasma glucose loading curves for each meal were calculated and fitted to an exponential function. The area under the curve (AUC) from 0 to 120 min and total digestible starch was used to calculate an in vitro glycaemic index (GI) value normalised against white bread. Microscopy was additionally used to examine cereal samples collected in vitro at different stages of gastric and duodenal digestion., Results: Where in vivo GI data were available (4 out of 6 cereal meals) no significant difference was observed between these values and the corresponding calculated in vitro GI value., Conclusion: It is possible to simulate an in vivo glycaemic response for cereals when the gastric emptying rate (duodenal loading) and kinetics of digestible starch hydrolysis in the duodenum are known.

Background and Aim of the Study: Homografts and the Ross procedure are recommended by many surgeons for aortic valve replacement (AVR) in young adults. The study aim was to monitor patient outcome over a 14-year period after implanting mechanical CarboMedics prosthetic heart valves in young adults with aortic valve disease., Methods: Between November 1987 and December 2000, 55 patients (42 males, 13 females; median age 33 years; range 15-40 years) each received a CarboMedics valve in the aortic position. All patients were included on a consecutive and non-selected basis. Concomitant surgery was performed in five patients. Anticoagulation was commenced on postoperative day 1. After discharge, patients were followed up by their cardiologist or general practitioner using questionnaires and telephone calls. Actuarial estimates of survival and freedom from morbid events were calculated using the Kaplan-Meier method., Results: No patient died during surgery. Complete follow up data were available for all patients; total follow up was 404 patient-years (pt-yr). The 30-day mortality rate was zero. Actuarial survival at 14 years was 90 +/- 4.9%, and actuarial freedom from all valve-related events 92 +/- 3.7%. No valve thrombosis or major bleeding events were identified. Linearized rates per 100 pt-yr were: embolism 0.25; paravalvular leakage 0.25; prosthetic endocarditis 0.25; and reoperation 0.50. There was no hemolysis, prosthetic valve dysfunction, or structural deterioration., Conclusion: Over a 14-year period, implantation of the CarboMedics prosthetic heart valve has proven to be an excellent solution for AVR in young adults with aortic valve disease.

Background: Operation for active infective endocarditis carries high mortality and morbidity rates, especially when the annulus is involved. Overall the literature favors the use of autograft and homograft valves because of better resistance to infection. In our clinic during the last 5 years we used an aggressive surgical approach to infective endocarditis in combination with implantation of mechanical or stented bioprosthetic devices., Methods: From 1994 to 1999, 50 adults with aortic and/or mitral valve endocarditis underwent valve replacement. The median age of the 36 men and 14 women was 58 years (range, 17 to 78 years). All patients had active endocarditis at the time of operation. Native valve endocarditis was present in 48 patients and prosthetic valve endocarditis was present in 2 patients. The aortic valve was affected in 24 patients, the mitral valve in 21 patients, and both the aortic and mitral valves in 5 patients. Two of the patients with mitral endocarditis also had infection of the tricuspid valve. Annular destruction was present in 24 patients (48%). The patients were treated with radical excision of all infected tissue. The annular defects were closed, if possible, with direct sutures. Otherwise, a reconstruction was performed. Follow-up was 100% complete with a median follow-up period of 45 months (range, 6 to 66 months)., Results: The procedures were performed without lethal bleeding complications. Early mortality was 12% and the actuarial survival at follow-up was 80%. In none of the patients who died was death related to the prosthetic valve or recurrence of the endocarditis. Only 1 patient (2%) developed recurrence of the infective endocarditis and was reoperated with a Ross procedure. Three and a half years later the patient developed severe valve insufficiency of the autograft and was operated again with implantation of a mechanical device., Conclusions: Native and prosthetic valve endocarditis can be treated successfully with aggressive surgical debridement and implantation of mechanical or stented bioprosthetic devices with a low risk of recurrent endocarditis.

Nine gallstone patients with normal gallbladder function as assessed by hepatobiliary scintigraphy were included. Fasting and postprandial duodenal motility were studied before and one month after an uncomplicated laparoscopic cholecystectomy. An ambulatory continuous pressure recording was obtained from 5 PM to 8 AM with a sampling frequency of 4 Hz. At 6 PM, the patients received a 1400-kJ standard meal. The size of the bile acid pool after cholecystectomy was measured according to the dilution principle using [C14]cholic acid as the marker. Preoperatively the migrating motor complex (MMC) cycle was 0.48/hr (quartiles 0.42-0.68) compared to 0.68/hr (0.43-0.77) postoperatively. This difference was not significant. An increase in the MMC cycle frequency was observed postoperatively in three patients, and a decrease was seen in four patients. The migration velocity was 5.61 cm/min (4.26-8.01) preoperatively and 7.16 cm/min (4.79-9.71) postoperatively, a difference that was not significant. The time period from meal ingestion to appearance of phase III was 297 min (218-431) at the preoperative examination and 443 min (192-494) at the postoperative examination. This difference was not significant. The size of the bile acid pool after cholecystectomy was 3.68 mmol (2.69-8.47) and was not significantly correlated to the frequency of the MMC cycle or the time period from food ingestion to phase III activity. It is concluded that in gallstone patients with a normally functioning gallbladder, cholecystectomy does not alter duodenal motility, which was not correlated to the size of the bile acid pool.

Background: The use of a mesh in transabdominal preperitoneal laparoscopic hernia repair (TAPP) caries the risk of late rejection or infectious complications related to the mesh. The aim of this study was to describe the extent of these complications., Methods: We performed a retrospective study of 500 consecutive patients with TAPP for inguinal hernia., Results: Late mesh rejection was observed in three patients at 5-19 months after surgery. The mesh was removed via a suprapubic midline incision. At 3-4 month's follow-up, none of the patients had recurrence of the hernia, even though no hernia repair had been done., Conclusion: Late mesh rejection is a potential complication of TAPP and has to be considered when choosing the surgical method of hernia repair.

Acute herniations through a posterolateral diaphragmatic defect (Bochdalek hernia) are rare in adults. Most of these hernias are on the left side causing gastrointestinal symptoms. We present af case of a Bochdalek hernia on the right side, where incarceration and distension of the stomach was followed by dyspnoea and haemoptysis. Aetiology, symptoms, diagnosis and treatment are discussed.