Significant individual variation between pathologists in the evaluation of colon cancer specimens after complete mesocolic excision

Background: After the introduction of complete mesocolic excision, a new pathological evaluation of the resected colon cancer specimen was introduced. This concept has quickly gained acceptance and is often used to compare surgical quality. The grading of colon cancer specimens is likely to depend on both surgical quality and the training of the pathologist. Objective: The purpose of this study was to validate the principles of the pathological evaluation of colon cancer specimens. Design: This was an exploratory study. Settings: The study was conducted in Aarhus, Denmark, and Leeds, United Kingdom. Patients: Colon cancers specimens were used. Main outcome measures: The agreement of gradings between participants was of interest. Four specialist GI pathologists and 2 abdominal surgeons evaluated 2 rounds of colon cancer specimens, each at 2 separate time points. Each round contained 50 specimens. After the first round, a protocol of detailed principles for the grading procedure was agreed on. Results from an experienced pathologist were considered as the reference results. Results: In the first round, the distribution of gradings between participants showed substantial variation. In the second round, the variation was reduced. Intraobserver agreement was mostly fair to good, whereas interobserver agreement was frequently poor. This did not significantly change from round 1 to round 2. Limitations: The small sample size of 100 specimens provided a very small number of specimens resected in the muscularis propria plane, which renders the evaluation of this group potentially unreliable. The evaluations were made on photos and not on fresh specimens. Conclusions: This study demonstrates significant variation in the pathological evaluation of colon cancer specimens. It demonstrates that it cannot be used in clinical studies, and care should be taken when comparing results between different hospitals

Thyroid Function and Body Weight: A Community-Based Longitudinal Study

OBJECTIVE: Body weight and overt thyroid dysfunction are associated. Cross-sectional population-based studies have repeatedly found that thyroid hormone levels, even within the normal reference range, might be associated with body weight. However, for longitudinal data, the association is less clear. Thus, we tested the association between serum thyrotropin (TSH) and body weight in a community-based sample of adult persons followed for 11 years. METHODS: A random sample of 4,649 persons aged 18-65 years from a general population participated in the DanThyr study in 1997-8. We included 2,102 individuals who participated at 11-year follow-up, without current or former treatment for thyroid disease and with measurements of TSH and weight at both examinations. Multiple linear regression models were used, stratified by sex and adjusted for age, smoking status, and leisure time physical activity. RESULTS: Baseline TSH concentration was not associated with change in weight (women, P = 0.17; men, P = 0.72), and baseline body mass index (BMI) was not associated with change in TSH (women, P = 0.21; men, P = 0.85). Change in serum TSH and change in weight were significantly associated in both sexes. Weight increased by 0.3 kg (95% confidence interval [CI] 0.1, 0.4, P = 0.005) in women and 0.8 kg (95% CI 0.1, 1.4, P = 0.02) in men for every one unit TSH (mU/L) increase. CONCLUSIONS: TSH levels were not a determinant of future weight changes, and BMI was not a determinant for TSH changes, but an association between weight change and TSH change was present

Long-term outcome of sacral neuromodulation for chronic refractory constipation

Purpose Sacral neuromodulation has been reported as a treatment for severe idiopathic constipation. This study aimed to evaluate the long-term effects of sacral neuromodulation by following patients who participated in a prospective, open-label, multicentre study up to 5 years. Methods Patients were followed up at 1, 3, 6, 12, 24, 36, 48 and 60 months. Symptoms and quality of life were assessed using bowel diary, the Cleveland Clinic constipation score and the Short Form-36 quality-of-life scale. Results Sixty-two patients (7 male, median age 40 years) underwent test stimulation, and 45 proceeded to permanent implantation. Twenty-seven patients exited the study (7 withdrawn consent, 7 loss of efficacy, 6 site-specific reasons, 4 withdrew other reasons, 2 lost to follow-up, 1 prior to follow-up). Eighteen patients (29%) attended 60-month follow-up. In 10 patients who submitted bowel diary, their improvement of symptoms was sustained: the number of defecations per week (4.1 ± 3.7 vs 8.1 ± 3.4, mean ± standard deviation, p < 0.001, baseline vs 60 months) and sensation of incomplete emptying (0.8 ± 0.3 vs 0.2 ± 0.1, p = 0.002). In 14 patients (23%) with Cleveland Clinic constipation score, improvement was sustained at 60 months [17.9 ± 4.4 (baseline) to 10.4 ± 4.1, p < 0.001]. Some 103 device-related adverse events were reported in 27 (61%). Conclusion Benefit from sacral neuromodulation in the long-term was observed in a small minority of patients with intractable constipation. The results should be interpreted with caution given the high dropout and complication rate during the follow-up period

Social inequality in cancer survivorship:Educational differences in health‐related quality of life among 27,857 cancer survivors in Denmark

BackgroundWith a growing population of cancer survivors in Denmark, the evaluation of health-related quality of life (HRQoL) has become increasingly important. We describe variations in HRQoL between educational groups in a national population of cancer survivors.MethodsWe conducted a cross-sectional questionnaire study among breast, prostate, lung, and colon cancer survivors diagnosed in 2010–2019 in Denmark. We used the EORTC QLQ-C30 to assess HRQoL including physical, role, emotional, cognitive, social functioning, and symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Information on educational level and clinical data were extracted from national registers and clinical databases. Levels of impaired functioning and severe symptoms were identified using newly established thresholds for clinical importance. Multivariate logistic regression was used to examine associations between education and HRQoL. All statistical tests were 2-sided.ResultsIn total, 27,857 (42%) participated in the study. Up to 72% and 75% of cancer survivors with short education (≤9 years) reported impaired functioning and severe symptoms, respectively. Cancer survivors with short compared to long education (&gt;12 years) were more likely to report impaired functioning and severe symptoms, with for example significantly higher odds ratios (ORs) for impaired physical function (breast OR = 2.41, 99% CI = 2.01–2.89; prostate OR = 1.81, 99% CI = 1.48–2.21; lung OR = 2.97, 99% CI = 1.95–4.57; and colon cancer OR = 1.69, 99% CI = 1.28–2.24).ConclusionsCancer survivors with short education are at greater risk of impaired HRQoL than survivors with long education 2–12 years after diagnosis. This underscores the need for systematic screening and symptom management in cancer aftercare, in order to reach all cancer survivors, also cancer survivors with short education

Blood-based biomarkers at large bowel endoscopy and prediction of future malignancies

Soluble cancer-related protein biomarker levels may be increased in subjects without findings at large bowel endoscopy performed due to symptoms associated with colorectal cancer. The present study focused on a possible association between increased biomarker levels in such subjects and subsequent development of malignant diseases. In a major study of 4,990 subjects undergoing large bowel endoscopy, 691 were without pathology and comorbidity. Plasma levels of TIMP-1, CEA, CA19-9, and YKL-40 were determined in samples collected just before endoscopy and compared with subsequent development of a malignant disease within a period of 7-8 years. The upper 90% limits of the reference levels of every single protein were used to differentiate between normal and increased levels. The levels were separated into three groups: 0, none of the biomarkers increased; 1, one biomarker increased; 2, two or more biomarkers increased. A total of 43 subjects developed a primary malignant disease in the observation period. Univariatly, increase of all four biomarkers was significantly associated with subsequent development of a malignant disease. A multivariate analysis showed that increased biomarker levels were associated with subsequent development of a malignant disease ( P = 0.002). The cumulative risk of developing malignant disease within the first 5 years after endoscopy was group 0, 3.3%; group 1, 5.8%; group 2, 7.8%. It is concluded that increased levels of plasma TIMP-1, CEA, CA19-9, and serum YKL-40 at large bowel endoscopy without findings may be associated with an increased risk of developing a subsequent malignant disease

MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer

Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67-4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types