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.

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.

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.

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

BACKGROUND: 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 coexistence and familial association of autoimmune disorders in PSC, and the influence of autoimmune co-morbidity on severe outcomes. METHOD: In a matched cohort study, 1,378 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, liver related death). Odds ratio (OR) of autoimmune disease was estimated by logistic regression. Fine & Gray competing risk regression estimated hazard ratios (HRs) for severe outcomes. RESULTS: Prevalence of non-IBD, non-autoimmune hepatitis (AIH), 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 for developing IBD, AIH 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 co-morbidity in PSC was not associated with poorer outcome, HR 0.96 (95%CI; 0.71-1.28). CONCLUSION: Individuals with PSC and their first-degree relatives had higher odds for autoimmune disease compared to matched comparators. This finding provides validation for prior genetic discoveries at a phenotypic level. Autoimmune comorbidity did not impact severe outcome.

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.

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.

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.

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.

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.

Endothelial basement membrane laminins - new players in mouse and human myoendothelial junctions and shear stress communication.

Basement membranes (BMs) are critical but frequently ignored components of the vascular system. Using high-resolution confocal imaging of whole-mount-stained mesenteric arteries, we identify integrins, vinculin, focal adhesion kinase (FAK) and several BM proteins including laminins as novel components of myoendothelial junctions (MEJs), anatomical microdomains that are emerging as regulators of cross-talk between endothelium and smooth muscle cells (SMCs). Electron microscopy revealed multiple layers of the endothelial BM that surround endothelial projections into the smooth muscle layer as structural characteristics of MEJs. The shear-responsive calcium channel TRPV4 is broadly distributed in endothelial cells and occurs in a proportion of MEJs where it localizes to the tips of the endothelial projections that are in contact with the underlying SMCs. In mice lacking the major endothelial laminin isoform, laminin 411 (Lama4-/-), which we have previously shown over-dilate in response to shear and exhibit a compensatory laminin 511 upregulation, localization of TRPV4 at the endothelial-SMC interface in MEJs was increased. Endothelial laminins do not affect TRPV4 expression, rather in vitro electrophysiology studies using human umbilical cord arterial endothelial cells revealed enhanced TRPV4 signalling upon culturing on an RGD-motif containing domain of laminin 511. Hence, integrin-mediated interactions with laminin 511 in MEJ structures unique to resistance arteries modulate TRPV4 localization at the endothelial-smooth muscle interface in MEJs and signalling over this shear-response molecule.

The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.

Innate lymphoid cells (ILCs) are considered innate counterparts of adaptive T cells; however, their common and unique transcriptional signatures in pediatric inflammatory bowel disease (pIBD) are largely unknown. Here, we report a dysregulated colonic ILC composition in pIBD colitis that correlates with inflammatory activity, including accumulation of naive-like CD45RA+CD62L- ILCs. Weighted gene co-expression network analysis (WGCNA) reveals modules of genes that are shared or unique across innate and adaptive lymphocytes. Shared modules include genes associated with activation/tissue residency, naivety/quiescence, and antigen presentation. Lastly, nearest-neighbor-based analysis facilitates the identification of "most inflamed" and "least inflamed" lymphocytes in pIBD colon with unique transcriptional signatures. Our study reveals shared and unique transcriptional signatures of colonic ILCs and T cells in pIBD. We also provide insight into the transcriptional regulation of colonic inflammation, deepening our understanding of the potential mechanisms involved in pIBD.

Colectomy in patients with ulcerative colitis is not associated to future diagnosis of primary sclerosing cholangitis.

BACKGROUND: Primary Sclerosing Cholangitis (PSC) is a hepatobiliary disease closely related to ulcerative colitis (UC). In PSC patients, colectomy has been linked to improved prognosis, especially following liver transplantation. This suggests an involvement of the gut-liver axis in PSC etiology. OBJECTIVE: We aimed to investigate the association between colectomy and the risk of future PSC in an epidemiological setting. METHOD: Through nationwide registers, we identified all adults diagnosed with UC in Sweden 1990-2018 and retrieved information on PSC diagnosis and colectomy. Within the UC cohort (n = 61,993 patients), we matched 5577 patients with colectomy to 15,078 without colectomy. Matching criteria were sex, age at UC onset (±5 years), year of UC onset (±3 years), and proctitis at the time of colectomy. Incidence rates of PSC per 1000-person year were calculated, and the Cox proportional hazard regression model estimated hazard ratios (HRs) for PSC until 31 December 2019. RESULTS: During the follow-up, 190 (3.4%) colectomized UC patients and 450 (3.0%) UC comparators developed PSC, yielding incidence rates of 2.6 and 2.4 per 1000 person-years (HR 1.07 [95% CI 0.90-1.28]). The cumulative incidence of colectomy decreased remarkably over calendar periods, but the cumulative incidence of PSC remained unchanged. The risk of developing PSC in colectomized versus comparators changed over time (HR 0.68 [95% CI; 0.48-0.96] in 1990-97 and HR 2.10 [95% CI; 1.37-3.24] in 2011-18). CONCLUSIONS: In UC patients, colectomy was not associated with a decreased risk of subsequent PSC. The observed differences in the risk of PSC development over calendar periods are likely due to changes in PSC-diagnosis and UC-treatment.

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.

A Randomized Controlled Clinical Trial of Transanal Irrigation Versus Conservative Treatment in Patients With Low Anterior Resection Syndrome After Rectal Cancer Surgery.

OBJECTIVE: The aim of the study was to evaluate transanal irrigation (TAI) as a treatment for low anterior resection syndrome (LARS). BACKGROUND: LARS is a bowel disorder that is common after sphincter preserving rectal cancer surgery. Despite symptomatic medical treatment of LARS many patients still experience bowel symptoms that may have a negative impact on quality of life (QoL). TAI is a treatment strategy, of which the clinical experience is promising but scientific evidence is limited. MATERIALS AND METHODS: A multicenter randomized trial comparing TAI (intervention) with conservative treatment (control) was performed. Inclusion criteria were major LARS, age above 18 years, low anterior resection with anastomosis and a defunctioning stoma as primary surgery, >6 months since stoma reversal, anastomosis without signs of leakage or stricture, and no signs of recurrence at 1-year follow-up. The primary endpoint was differences in bowel function at 12-month follow-up measured by LARS score, Cleveland Clinic Florida Fecal Incontinence Score, and 4 study-specific questions. The secondary outcome was QoL. RESULTS: A total of 45 patients were included, 22 in the TAI group and 23 in the control group. Follow-up was available for 16 and 22 patients, respectively. At 12 months, patients in the TAI group reported significantly lower LARS scores (22.9 vs 32.4; P =0.002) and Cleveland Clinic Florida Fecal Incontinence Score (6.4 vs 9.2; P =0.050). In addition, patients in the TAI group also scored significantly higher QoL [8 of 16 European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) QoL aspects] compared with the control group. CONCLUSIONS: The results confirm our clinical experience that TAI reduces symptoms included in LARS and improves QoL.