Non-Curative Treatment Choices in Colorectal Cancer: Predictors and Between-Hospital Variations in Denmark: A Population-Based Register Study.

BACKGROUND: Variations in treatment choices have been reported in colorectal cancer (CRC). In the context of national recommendations, we aimed to elucidate predictors and between-hospital variations in refraining from curatively intended surgery and adjuvant chemotherapy in potentially curable colorectal cancer. METHODS: A total of 34,116 patients diagnosed with CRC from 2009 to 2018 were included for analyses on non-curative treatment in this register-based study. Subsequently 8006 patients were included in analyses on adjuvant treatment. Possible predictors included patient-, disease-, socioeconomic- and perioperative-related factors. Logistic regressions were utilized to examine the predictors of a non-curative aim of treatment and no adjuvant chemotherapy. RESULTS: The predictors of non-curative treatment were high age, poor performance, distant metastases and being underweight. Predictors for no adjuvant treatment were high age, poor performance, kidney disease, postoperative complications and living alone. For both outcomes we found between-hospital variations to be present. CONCLUSIONS: Non-curative overall treatment and refraining from adjuvant chemotherapy were associated with well-known risk factors, but the former was also associated with being underweight and the latter was also associated with living alone. Marked between-hospital variations were found and should be examined further.

Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study.

INTRODUCTION: Management of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical management instead of surveillance strategy, there are between 54% and 82% of bowel resections without evidence of residual tumour or lymphatic spread. As surgical management entails risks of complications and surveillance strategy entails risks of residual tumour or recurrence, a clinical dilemma arises when choosing a management strategy. Shared decision-making is a concept that can be used in preference-sensitive decision-making to facilitate patient involvement and empowerment to facilitate active patient participation in the decision-making process. METHODS AND ANALYSIS: This study protocol describes our clinical multi-institutional, non-randomised, interventional phase II study at Danish surgical departments planned to commence in the second quarter of 2024. The aim of this study is to examine whether shared decision-making and using a patient decision aid in consultations affect patients' choice of management, comparing with retrospective data. The secondary aim is to investigate patients' experiences, perceived involvement, satisfaction, decision conflict and other outcomes using questionnaire feedback directly from the patients. ETHICS AND DISSEMINATION: There are no conflicts of interest for principal or local investigators in any of the study sites. All results will be published at Danish and international meetings, and in English language scientific peer-reviewed journals. Our study underwent evaluation by the Regional Committees on Health Research Ethics for Southern Denmark (file number 20232000-47), concluding that formal approval was not required for this kind of research. TRIAL REGISTRATION NUMBER: NCT05776381.

Endorectal Ultrasound Shear-Wave Elastography of Complex Rectal Adenoma and Early Rectal Cancer.

Purpose: To investigate the diagnostic performance of endorectal ultrasound (ERUS), shear-wave elastography (SWE), and magnetic resonance imaging (MRI) in patients with a complex rectal adenoma or an early rectal cancer, i.e., T1 or T2 adenocarcinoma in a clinical setting, and to evaluate the association between SWE and stromal fraction (SF) and apparent diffusion coefficient (ADC) and SF. Method: This prospective study included patients undergoing ERUS and SWE for a rectal tumor subsequently confirmed by histopathology to be an adenoma or a T1 or T2 adenocarcinoma. The accuracy of the imaging methods was assessed by comparing the T category as determined by ERUS and MRI with histopathology, which served as the gold standard. SF was assessed on surgical specimens. Results: A total of 86 patients were included. Of these, 62 patients had adenomas and 24 patients had carcinomas, of which 11 were T1 tumors and 13 were T2 tumors. ERUS and MRI yielded sensitivity, specificity, and accuracy of 0.79 and 0.73, 0.95 and 0.90, and 0.86 and 0.78, respectively, for discrimination between benign and malignant lesions. The area under the receiver operating characteristics curve for SWE was 0.88, and with a cut-off value of 40 kPa the sensitivity, specificity, and accuracy were 0.79, 0.89, and 0.86, respectively. There was a positive correlation between SF and SWE with a p-value of <0.001 and a negative correlation between SF and ADC with a p-value of 0.011. Conclusion: Both ERUS and MRI classified T categories with a high accuracy; however, ERUS classified more adenomas correctly than MRI. In this small population, SWE could differentiate an adenoma from early carcinoma. SF was correlated with both SWE and ADC, as increasing SF tended to yield higher SWE and lower ADC values.

Effectiveness of an expert assessment and individualised treatment compared with a minimal home-based exercise program in women with late-term shoulder impairments after primary breast cancer surgery: study protocol for a randomised controlled trial.

BACKGROUND: In breast cancer patients, late-term upper limb sequelae, such as shoulder pain and impaired shoulder function, remain common after primary breast cancer surgery. The aim of this trial is to evaluate whether an expert assessment of shoulder impairments, followed by an individualised treatment plan, is superior to a minimal physiotherapeutic rehabilitation program in reducing shoulder symptoms, among women with late-term shoulder impairments after primary breast cancer. METHODS/DESIGN: The study is designed as a stratified, parallel-group, assessor-blinded, randomised, controlled trial conducted in Denmark; 130 participants with late-term shoulder impairments 3-7 years after primary surgery for breast cancer will be recruited. Participants will be randomised (allocation 1:1) to either an expert assessment of shoulder impairments followed by an individualised treatment plan or to follow a minimal physiotherapeutic rehabilitation program delivered in a pamphlet. The primary outcome will be a change in shoulder pain and function from baseline to 12 weeks after initiating the treatment, as measured by the patient-reported outcome Shoulder Pain and Disability Index (SPADI) questionnaire. DISCUSSION: There has been an insufficient focus in research and clinical practice on late-term shoulder impairment in women following surgery for breast cancer. This trial will focus on interventions towards late-term shoulder impairments and is expected to provide evidence-based knowledge to physiotherapists and women about the management of shoulder pain and impaired shoulder function. TRIAL REGISTRATION: ClinicalTrials.gov NCT05277909. Registered on 11 March 2022.

The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer.

INTRODUCTION: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants. METHODS: We screened 98 patients aged 18-40 with CRC diagnosed in 2010-2013 for variants in MSH2, MSH6, MLH1, PMS2, EPCAM, APC, MUTYH, SMAD4, BMPR1A, STK11, PTEN, POLE, POLD1, NTHL1, AXIN2, MSH3, GREM1 and RNF43 using Next Generation Sequencing. Comparisons between patients' characteristics in patients with PGV, and patients without germline variants (NPGV) were analyzed. RESULTS: PGV were detected in twenty-four patients (24.5%), and twenty-one patients (21.1%) had variants in the mismatch repair (MMR) genes associated with LS. Variants in the APC and MUTYH genes were detected in 1% and 4%, respectively. Patients with NPGV had more advanced disease with adverse histopathological features. CONCLUSION: PGV was detected in one in four yCRC patients, and one in five yCRC patients had disease causing variants in the mismatch repair genes associated with LS.

The Impact of Patient Characteristics and Tumor Biology on the Accuracy of Preoperative Staging of Colon Cancer in Denmark. A Nationwide Cohort Study.

BACKGROUND: Colon cancer is a common disease in western populations. The aim of this study was to assess the impact of mismatch repair (MMR) deficiency and other patient and tumor characteristics on the accuracy of preoperative staging by comparing histopathological T- and N-categories of the resected specimen with the preoperative clinical stage in a nationwide cohort of patients treated for colon cancer by elective bowel resection with curative intent. METHODS: A register study of a cohort extracted from the Danish Colorectal Cancer Group (DCCG) database, which holds prospective data on all new cases of colon and rectum cancer in Denmark. Patients diagnosed with colon cancer and treated with an elective bowel resection with curative intent in the years 2016-2019 were analyzed. RESULTS: A total of 6102 patients were included (n = 3161 (52%) men and n = 2941 (48%) women) with a median age of 72 years (range 23-97 years). MMR was deficient in 24% of the patients and proficient in 76%. MMR deficiency, tumor sidedness and histopathological type were significant predictors of the accuracy of preoperative staging of colon cancer in univariate and multivariate analysis. MMR status in particular showed a strong impact on the risk of overstaging. CONCLUSIONS: MMR deficiency, but also tumor sidedness and to some degree histopathological type, impacted the accuracy of preoperative staging of colon cancer. MMR status should be taken into consideration in everyday clinical staging.

Can Ultrasound Elastography Discriminate between Rectal Adenoma and Cancer? A Systematic Review.

BACKGROUND: Rectal cancer is a common malignancy. Since the introduction of bowel-screening programs, the number of patients with advanced adenomas and early rectal cancer has increased. Despite improved diagnostics, the discrimination between rectal adenomas and early rectal cancer (i.e., pT1-T2) remains challenging. The purpose of this systematic review was to evaluate the diagnostic performance of endorectal ultrasound (ERUS) elastography in discriminating rectal adenomas from cancer. METHOD: Using PRISMA guidelines, a systematic search was performed on PubMed, Embase, and MEDLINE databases. Studies evaluating the primary staging of rectal adenomas and cancer using ERUS elastography were included. RESULTS: Six studies were identified; three evaluated the discrimination between adenomas and cancer; two evaluated adenomas and early rectal cancer (i.e., pT1-T2); one evaluated performance on different T categories. All studies reported increased diagnostic accuracy of ERUS elastography compared to ERUS. Sensitivity, specificity and accuracy ranged 0.93-1.00, 0.83-1.00 and 0.91-1.00, respectively, when discriminating adenomas from cancer. In the differentiation between adenomas and early rectal cancer, the sensitivity, specificity and accuracy were 0.82-1.00, 0.86-1.00 and 0.84-1.00, respectively. CONCLUSION: Elastography increases the accuracy of ERUS and may provide valuable information on malignant transformation of rectal lesions.

Long-term anorectal function in rectal cancer patients treated with chemoradiotherapy and endorectal brachytherapy.

AIM: The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer. METHODS: This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores. RESULTS: Thirteen RCPs (12 men, median age 68 years, range 52-92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8 years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64 years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8 mmHg (25.7-105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188 mmHg (103-248) (P < 0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P = 0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P < 0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P = 0.56). CONCLUSION: Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.

Sociodemographic characteristics of nonparticipants in the Danish colorectal cancer screening program: a nationwide cross-sectional study.

INTRODUCTION: Fecal occult blood tests are recommended for colorectal cancer (CRC) screening in Europe. Recently, the fecal immunochemical test (FIT) has come into use. Sociodemographic differences between participants and nonparticipants may be less pronounced when using FIT as there are no preceding dietary restrictions and only one specimen is required. The aim of this study was to examine the associations between sociodemographic characteristics and nonparticipation for both genders, with special emphasis on those who actively unsubscribe from the program. METHODS: The study was a national, register-based, cross-sectional study among men and women randomized to be invited to participate in the prevalence round of the Danish CRC screening program between March 1 and December 31, 2014. Prevalence ratios (PRs) were used to quantify the association between sociodemographic characteristics and nonparticipation (including active nonparticipation). PRs were assessed using Poisson regression with robust error variance. RESULTS: The likelihood of being a nonparticipant was highest in the younger part of the population; however, for women, the association across age groups was U-shaped. Female immigrants were more likely to be nonparticipants. Living alone, being on social welfare, and having lower income were factors that were associated with nonparticipation among both men and women. For both men and women, there was a U-shaped association between education and nonparticipation. For both men and women, the likelihood of active nonparticipation rose with age; it was lowest among non-western immigrants and highest among social welfare recipients. CONCLUSION: Social inequality in screening uptake was evident among both men and women in the Danish CRC screening program, even though the program is free of charge and the screening kit is based on FIT and mailed directly to the individuals. Interventions are needed to bridge this gap if CRC screening is to avoid aggravating existing inequalities in CRC-related morbidity and mortality.