Postoperative complications and emergency surgeries in colorectal cancer patients <50 years-a national cohort study.

AIM: The incidence of colorectal cancer (CRC) in Sweden is increasing in individuals <50 years. This study aimed to examine differences in postoperative 30-day complications and rate of emergency surgeries in CRC patients <50 years at diagnosis compared to older age groups since population-based research on this topic is scarce. METHOD: This population-based study included data from the Swedish Colorectal Cancer Registry for patients undergoing CRC resection between 2010 and 2018. Bivariate analysis and logistic regression were used to analyse the relationship between age groups (<50, 50-79 and ≥80 years) and probability of postoperative 30-day complications adjusted for gender, tumour localization, neoadjuvant (chemo)radiotherapy and American Society of Anesthesiologists score. RESULTS: In total 33 320 patients were included. Patients <50 years had a lower American Society of Anesthesiologists score, more advanced tumours and received more neoadjuvant treatment. Emergency surgeries were less common in the youngest age group (P < 0.001) as well as overall postoperative 30-day complications: ORadj 0.84 (95% CI 0.74-0.96) compared to those ≥80 years. Surgical complications were more common in age groups <50 and 50-79 years (16.5% and 16.9% respectively) compared to patients ≥80 years (14.1%) (P < 0.001). Anastomotic leakage and intra-abdominal infections were more frequent in patients <50 years (5.7% and 3.5% respectively) compared to age groups 50-79 years (5.1% and 2.8% respectively) and ≥80 years (3.5% and 2.1% respectively) (P < 0.001). Wound infections were more common in the two youngest age groups compared to patients ≥80 years (5.3% vs. 3.7% respectively) (P < 0.001). CONCLUSION: Colorectal cancer patients <50 years and 50-79 years had a higher proportion of surgical complications regarding anastomotic leakage, intra-abdominal infections and wound infections but lower overall postoperative complications. The incidence of surgical emergencies was highest amongst patients ≥80 years. Postoperative diagnostic workup in symptomatic individuals <50 years is warranted.

Preoperative use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diuretics increases the risk of dehydration after ileostomy formation: population-based cohort study.

BACKGROUND: Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs affecting the homeostasis. The aim of the study was to assess the risk of dehydration after ileostomy formation in patients treated with angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or diuretics. METHOD: This nationwide population-based cohort study used data derived from the Colorectal Cancer Data Base of several Swedish healthcare registers. The study included all patients operated on with elective anterior resection and temporary ileostomy for rectal cancer clinically staged I-III in Sweden in 2007-2016. Exposure was at least two dispensations of ACEI, ARB or diuretics within 1 year prior to surgery. Outcome was 90-day readmission due to dehydration including acute renal failure. RESULTS: In total, 3252 patients were included with 1173 (36.1%) exposed to ACEI, ARB or diuretics. The cumulative incidence for 90-day readmission due to dehydration was 29.0% (151 of 520) for exposed versus 13.8% (98 of 712) for unexposed. The proportion of readmissions due to any reason was 44.3% (520 of 1173) for exposed compared to 34.2% (712 of 2079) for unexposed. The incidence rate ratio for readmission due to dehydration was 2.83 (95% c.i. 2.21 to 3.63, P < 0.001). The hazard rate ratio was 2.45 (95% c.i. 1.83 to 3.27, P < 0.001) after adjusting for age, gender and comorbidity. CONCLUSION: Medication with ACEI, ARB or diuretics defines a vulnerable patient group with increased risk of readmission due to dehydration after ileostomy formation.

Autoimmune diseases in primary sclerosing cholangitis and their first-degree relatives.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel disease (IBD). However, there is limited overlap between IBD and PSC risk genes, but a stronger association between PSC and other autoimmune conditions. We aimed to assess the coexistence and familial association of autoimmune disorders in PSC, and the influence of autoimmune comorbidity on severe outcomes. APPROACH AND RESULTS: In a matched cohort study, 1378 individuals with PSC and 13,549 general population comparators and their first-degree relatives were evaluated. National registries provided data on diagnoses and outcomes (liver transplantation, hepatobiliary cancer, and liver-related death). The OR of autoimmune disease was estimated by logistic regression. The Fine and Gray competing risk regression estimated HRs for severe outcomes. The prevalence of non-IBD, non-autoimmune hepatitis, and autoimmune disease was 18% in PSC and 11% in comparators, OR: 1.77 (95% CI: 1.53-2.05). Highest odds were seen for celiac disease [OR: 4.36 (95% CI: 2.44-7.49)], sarcoidosis [OR: 2.74 (95% CI: 1.29-5.33)], diabetes type 1 [OR: 2.91 (95% CI: 2.05-4.05)], and autoimmune skin disease [OR: 2.15 (95% CI: 1.52-2.96)]. First-degree relatives of individuals with PSC had higher odds of developing IBD, autoimmune hepatitis, and any autoimmune disease than relatives of the comparators [OR: 3.25 (95% CI: 2.68-3.91); OR: 5.94 (95% CI: 2.82-12.02); OR: 1.34 (95% CI: 1.19-1.50)]. Autoimmune comorbidity in PSC was not associated with poorer outcomes [HR: 0.96 (95% CI: 0.71-1.28)]. CONCLUSIONS: Individuals with PSC and their first-degree relatives had higher odds of autoimmune disease compared to matched comparators. This finding provides validation for prior genetic discoveries at a phenotypic level. Autoimmune comorbidity did not impact severe outcomes.

Income disparities in loss in life expectancy after colon and rectal cancers: a Swedish register-based study.

BACKGROUND: Differences in the prognosis after colorectal cancer (CRC) by socioeconomic position (SEP) have been reported previously; however, most studies focused on survival differences at a particular time since diagnosis. We quantified the lifetime impact of CRC and its variation by SEP, using individualised income to conceptualise SEP. METHODS: Data included all adults with a first-time diagnosis of colon or rectal cancers in Sweden between 2008 and 2021. The analysis was done separately for colon and rectal cancers using flexible parametric models. For each cancer and income group, we estimated the life expectancy in the absence of cancer, the life expectancy in the presence of cancer and the loss in life expectancy (LLE). RESULTS: We found large income disparities in life expectancy after a cancer diagnosis, with larger differences among the youngest patients. Higher income resulted in more years lost following a cancer diagnosis. For example, 40-year-old females with colon cancer lost 17.64 years if in the highest-income group and 13.68 years if in the lowest-income group. Rectal cancer resulted in higher LLE compared with colon cancer. Males lost a larger proportion of their lives. All patients, including the oldest, lost more than 30% of their remaining life expectancy. Based on the number of colon and rectal cancer diagnoses in 2021, colon cancer results in almost double the number of years lost compared with rectal cancer (24 669 and 12 105 years, respectively). CONCLUSION: While our results should be interpreted in line with what individualised income represents, they highlight the need to address inequalities.

Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer: A phase I and III open label randomized controlled registry-based clinical trial protocol.

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF.

Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142-/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142-/low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.

Long-term prescribed drug use in stage I-III rectal cancer patients in Sweden, with a focus on bowel-regulating drugs after surgical and oncological treatment.

PURPOSE: To describe long-term prescribed drug use after rectal cancer treatment. METHODS: We identified 12,871 rectal cancer patients without distant metastasis between 2005 and 2016 and 64,341 matched population comparators using CRCBaSe (a Swedish nationwide register linkage of colorectal cancer patients). Mean defined daily doses (DDDs) of drug dispensing during relapse-free follow-up were calculated by Anatomical Therapeutic Chemical drug categories. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) from negative binomial regression were used to compare drug dispensing between patients and comparators. RESULTS: The overall pattern of drug dispensing was similar among cancer survivors and comparators, although patients had higher mean DDDs of drugs regulating the digestive system. Excess dispensing of drugs for constipation (IRR, 3.35; 95% CI, 3.12-3.61), diarrhea (IRR, 6.43; 95% CI, 5.72-7.22), functional gastrointestinal disorders (IRR, 3.78; 95% CI, 3.15-4.54), and vitamin and mineral supplements (IRR, 1.37; 95% CI, 1.24-1.50) was observed up to 10 years after surgery. Treatment with Hartmann's procedure was associated with higher dispensing rates of digestive drugs compared to surgery with anterior resection and abdominoperineal resection but the association was attributed to higher use of diabetic drugs. Additionally, excess digestive drug dispensing was associated with more advanced cancer stage but not with (chemo)radiotherapy treatment. CONCLUSIONS: Excess drug use after rectal cancer is primarily driven by bowel-regulating drugs and is not modified by surgical or oncological treatment. IMPLICATIONS FOR CANCER SURVIVORS: The excess use of bowel-regulating drugs after rectal cancer indicated long-standing postsurgical gastrointestinal morbidity and need of prophylaxis. Reassuringly, no excess use of other drug classes was noted long term.

Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity.

Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived.

Validity assessment of the POLARS score tool in the prediction of post rectal cancer surgery LARS score in a population-based Swedish cohort.

OBJECTIVE: Low anterior resection syndrome (LARS) is one of the most common functional impairments after rectal cancer surgery with a high impact on quality of life. The Pre-Operative LARS score (POLARS) nomogram and its online tool has been developed to predict the degree of postoperative LARS. The aim of this study was to analyse how accurately the POLARS score could predict LARS scores when compared with actual patient-reported LARS (PR-LARS) scores in a population-based Swedish cohort. DESIGN: This retrospective cohort study included patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm County and were identified using the Swedish Colorectal Cancer Registry (SCRCR). Information regarding preoperative risk factors, patient and treatment characteristics, and presence of LARS postoperatively were collected from patient charts, SCRCR and patient questionnaires. The POLARS model formula was used to predict LARS scores, which then were compared with the actual PR-LARS scores. Individual LARS score differences between the two estimates were shown with a modified Bland-Altman plot of difference. RESULTS: The cohort included 477 patients, of whom 359 (75%) of patients were categorised as having no/minor LARS based on the POLARS score. The correctly identified patients by the POLARS score were 80/255 (31%) in the major LARS group and 184/222 (83%) no/minor LARS group. The sensitivity was 31% for major LARS and the positive predictive value was 68%. CONCLUSION: The POLARS score has a low sensitivity for major LARS in this Swedish cohort. Other methods to predict the risk of LARS need to be developed.

Despite multi-disciplinary team discussions the socioeconomic disparities persist in the oncological treatment of non-metastasized colorectal cancer.

BACKGROUND: The introduction of national guidelines should eliminate previously observed associations between socioeconomic status (SES) and colorectal cancer treatment. The aim of the study was to investigate whether inequalities remain. METHODS: CRCBaSe, a register-linkage originating from the Swedish Colorectal Cancer Registry, was used to identify information on patient and tumour characteristics, for 83,460 patients with stage I-III disease diagnosed 2008-2021. SES was measured as disposable income (quartiles) and the highest level of education. Outcomes of interest were emergency surgery, multidisciplinary team (MDT) conference discussion, and oncological treatment. Differences in treatment between SES groups were explored using multivariable logistic regression adjusted for year of diagnosis, age at diagnosis, sex, civil status, comorbidities, tumour location and stage. RESULTS: Patients in the highest income quartile had a lower risk of emergency surgery (OR 0.73 95%CI 0.68-0.80), a higher chance of being discussed at the preoperative (OR 1.39 95%CI 1.28-1.51) and postoperative MDT (OR 1.41 95%CI 1.30-1.53), receiving neoadjuvant (OR 1.15 95%CI 1.06-1.25) and adjuvant treatment (OR 2.04 95%CI 1.88-2.20). Higher education level increased the odds of MDT discussion but was not associated with oncological treatment. The proportion of patients discussed at the MDT increased, with almost all patients discussed since 2016. Despite this, treatment differences remained when patients diagnosed since 2016 were analysed separately. CONCLUSION: There were significant differences in how patients with different SES were treated for colorectal cancer. Further action is required to investigate the drivers of these differences as well as their impact on mortality and, ultimately, eliminate the inequalities.

Combined associations of a healthy lifestyle and body mass index with colorectal cancer recurrence and survival: a cohort study.

PURPOSE: Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a healthy lifestyle and body mass index on prognosis following CRC diagnosis. METHODS: Treatment and follow-up data were collected from the patient files of 1098 participants from the Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan-Meier method and Cox proportional hazards models adjusted for age, sex, and educational level. RESULTS: Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0-1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score 4 (most healthy). Patients with the healthiest lifestyle (HL score 4) compared to the least healthy (HL score 0-1) had an improved recurrence-free survival (HL 4 vs HL 0-1, HRadj 0.51 (95% CI 0.31-0.83) and overall survival (HL 4 vs HL 0-1, HRadj 0.52 (95% CI 0.38-0.70). CONCLUSION: Adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I-III CRC.

Incidence of adhesive small bowel obstruction after surgery for colorectal cancer in Sweden 2007-2016.

AIM: Population-based data on incidence and risk factors of adhesive small bowel obstruction (SBO) are limited. The aims of this study were to assess the risk of SBO and SBO surgery after bowel resection for colorectal cancer (CRC) and to assess whether this risk is modified by minimally invasive surgery (MIS) and radiotherapy in a retrospective national study. METHODS: CRCBaSe, a nationwide register linkage originating from the Swedish Colorectal Cancer Register, was used to identify Stage I-III CRC patients who underwent resection in 2007-2016, with follow-up throughout 2017. Matched CRC-free comparators (1:6) were included as a reference of SBO and SBO surgery incidence. The association between MIS and preoperative radiotherapy and the incidence rate of SBO was evaluated in adjusted multivariable Cox regression models. RESULTS: Among 33 632 CRC patients and 198 649 comparators, the 5-year cumulative incidence of SBO and SBO surgery was 7.6% and 2.2% among patients and 0.6% and 0.2% among comparators, with death as a competing risk. In all patients, MIS was associated with a reduced incidence of SBO (hazard ratio [HR] 0.7, 95% CI 0.6-0.8) and SBO surgery (HR 0.5, 95% CI 0.3-0.7). In rectal cancer patients, radiotherapy was associated with an increased incidence of SBO (HR 1.6, 95% CI 1.4-1.8) and SBO surgery (HR 1.7, 95% CI 1.3-2.3). DISCUSSION: Colorectal cancer surgery is associated with a marked increase in risk of SBO, compared with the general population. The incidence is further increased if open surgery or radiotherapy is performed.

The prognostic significance of microsatellite instability in colorectal cancer: a Swedish multi-center study.

PURPOSE: About 10 to 15% of patients with sporadic colorectal cancer display mutations in DNA mismatch repair (MMR) genes shown as microsatellite instability (MSI). Previous reports of colorectal cancer (CRC) indicate a better prognosis for patients with MSI tumors compared to patients with microsatellite stable (MSS) tumors. In this study, our aim was to investigate whether MSI is an independent prognostic factor in CRC. PATIENTS AND METHODS: Patients with stage I-III colorectal cancer and subject to curative surgery during 2002-2006 in the Swedish low-risk colorectal cancer study group cohort were eligible for inclusion. Deficient MMR (dMMR) status was analyzed by immunohistochemistry (IHC) and/or by MSI testing with polymerase chain reaction (PCR). Prognostic follow-up and treatment data were retrieved from patient records. Statistical analyses to assess MSI-status and prognosis were done using logistic regression and survival analyses using the Kaplan-Meier method and Cox regression hazards models adjusted for age, sex, stage, comorbidity, and tumor location. RESULTS: In total, 463 patients were included, MSI high tumors were present in 66 patients (14%), and the remaining 397 were MSS/MSI low. Within 6 years, distant recurrences were present in 9.1% and 20.2% (P = 0.049), and death occurred in 25.8% and 31.5% in MSI and MSS patients, respectively. There was no statistically significant difference in overall mortality (HR 0.80, 95% CI 0.46-1.38), relapse-free survival (HR 0.82, 95% CI 0.50-1.36), or cancer-specific mortality (HR 1.60, 95% CI 0.73-3.51). CONCLUSION: Despite distant metastases being less common in patients with MSI, there was no association between MSI and overall, relapse-free, or cancer-specific survival.

CRCBaSe: a Swedish register-based resource for colorectal adenocarcinoma research.

OBJECTIVES: To facilitate high-quality register-based research on colorectal cancer (CRC) in Sweden by constructing a database consisting of CRC patients, matched comparators, and relatives. MATERIAL AND METHODS: Patients with adenocarcinoma in the colon and/or rectum were identified in the Swedish Colorectal Cancer Register, a nationwide quality-of-care register. For each patient, six comparators from the general population were matched on birth year, sex, year of CRC diagnosis, and county. Comparators were free from CRC at the time of matching, but could later become cases. For both patients and comparators, first-degree relatives (parents, siblings, and children) were identified. Information from nationwide population-based registers was retrieved and linked to each individual in the database using the personal identification number unique to all Swedish residents. RESULTS: A total of 76,831 CRC patients diagnosed between 1995 and 2016 were identified (51% colon, 49% rectal; before 2007 only rectal cancer patients were included). Among all patients, 37% were stage I-II, 22% stage III, and 22% stage IV. The median follow-up time was 11.9 years (inter-quartile range, IQR: 8.6-15.3). Together with comparators and relatives, the database contains 2,413,139 individuals with information on demographics, dates and causes of death, in- and outpatient healthcare records, cancer diagnoses, prescribed and dispensed drugs, childbirths (among women), and social security information (such as sick leave and early retirement). CONCLUSION: The Colorectal Cancer Database Sweden (CRCBaSe) is a large and unique register-based data research platform, which opens up for clinically important, large epidemiological studies with innovative design in the field of colorectal adenocarcinoma.

Colectomy reconstruction for ulcerative colitis in Sweden and England: a multicenter prospective comparison between ileorectal anastomosis and ileal pouch-anal anastomosis after colectomy in patients with ulcerative colitis. (CRUISE-study).

BACKGROUND: There are no prospective trials comparing the two main reconstructive options after colectomy for Ulcerative colitis, ileal pouch anal anastomosis and ileorectal anastomosis. An attempt on a randomized controlled trial has been made but after receiving standardized information patients insisted on choosing operation themselves. METHODS: Adult Ulcerative colitis patients subjected to colectomy eligible for both ileal pouch anastomosis and ileorectal anastomosis are asked to participate and after receiving standardized information the get to choose reconstructive method. Patients declining reconstruction or not considered eligible for both methods will be followed as controls. The CRUISE study is a prospective, non-randomized, multi-center, open-label, controlled trial on satisfaction, QoL, function, and complications between ileal pouch anal anastomosis and ileorectal anastomosis. DISCUSSION: Reconstruction after colectomy is a morbidity-associated as well as a resource-intensive activity with the sole purpose of enhancing function, QoL and patient satisfaction. The aim of this study is to provide the best possible information on the risks and benefits of each reconstructive treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05628701.

Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case-Control Study.

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.

Low-dose aspirin use and colorectal cancer survival in 32,195 patients-A national cohort study.

BACKGROUND: Results from previous studies indicate that use of aspirin may improve colorectal cancer (CRC) survival. The aim of this study was to assess whether use of aspirin influences overall survival or CRC-specific survival in an unselected cohort of patients diagnosed with CRC. METHODS: The study was performed using the Colorectal Cancer Data Base Sweden (CRCBaSe), a mega-linkage originating from the Swedish Colorectal Cancer Register, with additional linkages to other national health care registers. All patients diagnosed with primary CRC stage I-III treated with curative surgery, aged 18-85 years at diagnosis, from 2007 through 2016 were identified. Information on low-dose aspirin use was extracted from the Swedish Prescribed Drug Register. Exposure was defined as dispensed prescription for at least 6 months. Aspirin exposure was analyzed at the time of surgery (yes/no) and as a time-varying exposure during follow-up. Follow-up was restricted to a maximum 6 years, to model 5-year survival. Cox regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Adjustments were performed for sex, age, year of diagnosis, Charlson comorbidity index, hypertension, and ASA score as potential confounders. RESULTS: A total of 32,195 patients diagnosed with CRC were included. 6764 (21%) were exposed to aspirin at the time of CRC surgery. The median time of follow-up was 4.2 years. Aspirin use at the time of surgery was not associated with all-cause (adjusted HR = 1.03, 95% CI: 0.97-1.08) nor CRC-specific mortality (adjusted HR = 0.99, 95% CI: 0.91-1.07). Aspirin use during follow-up was associated with increased all-cause (adjusted HR = 1.09, 95% CI: 1.04-1.15) but not CRC-specific mortality (adjusted HR = 0.98, 95% CI: 0.91-1.06). A CRC-specific effect associated with aspirin was noted from approximately 3 years following surgery. CONCLUSIONS: In this large nation-wide cohort study there was no convincing association between aspirin use after CRC and OS or CRC-specific survival.

Long-term opioid use following bicycle trauma: a register-based cohort study.

PURPOSE: Chronic opioid use is a significant public health burden. Orthopaedic trauma is one of the main indications for opioid prescription. We aimed to assess the risk for long-term opioid use in a healthy patient cohort. METHODS: In this matched cohort study, bicycle trauma patients from a Swedish Level-I-Trauma Centre in 2006-2015 were matched with comparators on age, sex, and municipality. Information about dispensed opioids 6 months prior until 18 months following the trauma, data on injuries, comorbidity, and socioeconomic factors were received from national registers. Among bicycle trauma patients, the associations between two exposures (educational level and injury to the lower extremities) and the risk of long-term opioid use (> 3 months after the trauma) were assessed in multivariable logistic regression models. RESULTS: Of 907 bicycle trauma patients, 419 (46%) received opioid prescriptions, whereof 74 (8%) became long-term users. In the first quarter after trauma, the mean opioid use was significantly higher in the trauma patients than in the comparators (253.2 mg vs 35.1 mg, p < 0.001) and fell thereafter to the same level as in the comparators. Severe injury to the lower extremities was associated with an increased risk of long-term opioid use [OR 4.88 (95% CI 2.34-10.15)], whereas high educational level had a protecting effect [OR 0.42 (95% CI 0.20-0.88)]. CONCLUSION: The risk of long-term opioid use after a bicycle trauma was low. However, opioids should be prescribed with caution, especially in those with injury to lower extremities or low educational level.

Sex differences in metastatic surgery following diagnosis of synchronous metastatic colorectal cancer.

The aim was to investigate gender differences in the likelihood to receive metastatic surgery, and to compare overall survival between men and women, among patients with synchronous metastatic colorectal cancer (mCRC) in a population-based setting. All Swedish adult patients diagnosed with synchronous mCRC in 2007-2016 were identified using the nationwide colorectal cancer database (CRCBaSe). Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression, comparing the odds of receiving treatment. The Kaplan-Meier method was used to calculate survival proportions and Cox regression models to estimate hazard ratios (HRs) and 95% CIs of all-cause mortality rates. All multivariable models were adjusted for age, ASA score, Charlson comorbidity index, year of diagnosis, location of primary tumor and single or multiple metastatic locations. A total of 12 201 patients met the study criteria. Women received 23% less metastatic surgery for mCRC (adjusted OR = 0.77, CI:0.69-0.86) and experienced a slightly higher mortality following diagnosis (adjusted HR = 1.09, CI:1.05-1.14). In analyses restricted to patients who received metastatic surgery, no significant differences in mortality were found. In conclusion, this population-based study showed that women less often received metastatic surgery of mCRC and experienced slightly higher all-cause mortality compared with men. The differences persisted despite adjustments of patient and cancer characteristics. Gender differences in receiving treatment are unacceptable if the underlying explanation cannot be motivated. Further studies are needed to understand if the differences are based on sex (i.e., biology) or gender (including clinically unmotivated differences in treatment approach).