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Previous solid organ transplantation has been associated with worse survival among colorectal cancer (CRC) patients. This study investigates the contribution of CRC characteristics and treatment-related factors to the differential survival. Using the Swedish register-linkage CRCBaSe, all patients with solid organ transplantation before CRC diagnosis were identified and matched with non-transplanted CRC patients. Associations between transplantation history and clinical CRC factors and survival were estimated using the Kaplan-Meier estimator and logistic, multinomial, and Cox regression, respectively. Ninety-eight transplanted and 474 non-transplanted CRC patients were followed for 5 years after diagnosis. Among patients with stage I-III cancer, transplanted patients had lower odds of treatment with abdominal surgery [odds ratio (OR):0.27, 95% confidence interval (CI):0.08–0.90], than non-transplanted patients. Among those treated with surgery, transplanted colon cancer patients had lower odds of receiving adjuvant chemotherapy (OR:0.31, 95% CI:0.11–0.85), and transplanted rectal cancer patients had higher rate of relapse (hazard ratio:9.60, 95% CI:1.84–50.1), than non-transplanted patients. Five-year cancer-specific and overall survival was 56% and 35% among transplanted CRC patients, and 68% and 57% among non-transplanted. Accordingly, transplanted CRC patients were treated less intensely than non-transplanted patients, and had worse cancer-specific and overall survival. These patients might benefit from multidisciplinary evaluation including transplantation specialists.

Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Abstract 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.

Abstract Background Only a limited proportion of patients with metastatic colorectal cancer (mCRC) receives metastatic surgery (including local ablative therapy). The aim was to investigate whether hospital volume and hospital level were associated with the chance of metastatic surgery. Methods This national cohort retrieved from the CRCBaSe linkage included all Swedish adult patients diagnosed with synchronous mCRC in 2009–2016. The association between annual hospital volume of incident mCRC patients and the chance of metastatic surgery, and survival, were assessed using logistic regression and Cox regression models, respectively. Hospital level (university/non-university) was evaluated as a secondary exposure in a similar manner. Both uni- and multivariable (adjusted for sex, age, Charlson comorbidity index, year of diagnosis, cancer characteristics and socioeconomic factors) models were fitted. Results A total of 1,674 (17%) out of 9,968 mCRC patients had metastatic surgery. High hospital volume was not associated with increased odds of metastatic surgery after including hospital level in the model, whereas hospital level was (odds ratio (OR) (95% confidence interval (CI)): 1.94 (1.68–2.24)). All-cause mortality was lower in university versus non-university hospitals (hazard ratio (95% CI): 0.83 (0.78–0.88)). Conclusions Patients with mCRC initially cared for by a university hospital experienced a greater chance to receive metastatic surgery and had superior overall survival. High hospital volume in itself was not associated with a greater chance to receive metastatic surgery nor a greater survival probability. Additional efforts should be imposed to provide more equal care for mCRC patients across Swedish hospitals.

Background and purpose: Neoadjuvant short-course radiotherapy (SCRT) followed by full-dose systemic chemotherapy is an established treatment modality in locally advanced rectal cancer (LARC). Until recently, SCRT has been exclusively delivered with photons. Proton beam therapy (PBT) may minimize acute toxicity, which in turn likely impacts favorably on the tolerability to subsequent chemotherapy. The aim of this study is a dosimetric comparison between SCRT with photons and protons in the randomized phase II trial PRORECT (NCT04525989). Materials and methods: From June 2021 to June 2022, twenty consecutive patients with LARC have been treated according to study protocol. For each patient, both a VMAT and a PBT treatment plans have been generated and compared pairwise. Results: Dose-volume histogram (DVH) analysis revealed that SCRT with protons significantly reduced radiation dose to pelvic organs at risk including bladder, bones, and bowel in comparison to SCRT with photons. Photon and proton treatment plans had equivalent conformity and homogeneity indexes. Conclusion: Preoperative SCRT with protons offers a significant reduction of radiation dose to normal tissues compared with current photon-based radiotherapy technique. Demonstrated dosimetric advantages may translate into measurable clinical benefits in patients with LARC. Clinical implications of the dosimetric superiority of SCRT with protons will be presented in the coming reports from the PRORECT trial.

Previous solid organ transplantation has been associated with worse survival among colorectal cancer (CRC) patients. This study investigates the contribution of CRC characteristics and treatment-related factors to the differential survival. Using the Swedish register-linkage CRCBaSe, all patients with solid organ transplantation before CRC diagnosis were identified and matched with non-transplanted CRC patients. Associations between transplantation history and clinical CRC factors and survival were estimated using the Kaplan-Meier estimator and logistic, multinomial, and Cox regression, respectively. Ninety-eight transplanted and 474 non-transplanted CRC patients were followed for 5 years after diagnosis. Among patients with stage I-III cancer, transplanted patients had lower odds of treatment with abdominal surgery [odds ratio (OR):0.27, 95% confidence interval (CI):0.08-0.90], than non-transplanted patients. Among those treated with surgery, transplanted colon cancer patients had lower odds of receiving adjuvant chemotherapy (OR:0.31, 95% CI:0.11-0.85), and transplanted rectal cancer patients had higher rate of relapse (hazard ratio:9.60, 95% CI:1.84-50.1), than non-transplanted patients. Five-year cancer-specific and overall survival was 56% and 35% among transplanted CRC patients, and 68% and 57% among non-transplanted. Accordingly, transplanted CRC patients were treated less intensely than non-transplanted patients, and had worse cancer-specific and overall survival. These patients might benefit from multidisciplinary evaluation including transplantation specialists. [ABSTRACT FROM AUTHOR]

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT–) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation. Lay Summary: Radiation therapy (RT) for rectal cancer before surgery reduces the risk of cancer recurrence, but can cause injuries to the pelvic bone. Despite the high morbidity from RT-caused skeletal injuries, predictive and preventive measures are lacking. How these bone injuries are reflected by bone biomarkers measured in serum is largely unknown. The aim of this study was to measure serum bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. The study group included 47 women with rectal cancer treated with surgery ± preoperative RT. Pelvic magnetic resonance imaging was used for detection of skeletal injury. The bone biomarkers sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr after surgery. Sixteen of 36 (44%) irradiated women had radiation-caused bone injuries and were compared to 31 women without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-caused bone injuries. In summary, bone markers may be of interest for future research on fracture prediction or preventive measures in women prone to radiation-caused bone injury. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundImpairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (

BackgroundEpidemiological studies have shown a potential association between sex hormones and colorectal cancer. The risk of colorectal cancer in breast cancer patients who may have been exposed to increased levels of endogenous sex hormones and/or exogenous sex hormones (e.g. anti-hormonal therapy) has not been thoroughly evaluated.MethodsUsing the National Swedish Cancer Register we established a population-based prospective cohort of breast cancer patients in women diagnosed in Sweden between 1961 and 2010. Subsequent colorectal cancers were identified from the same register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs) were used to estimate the risk of colorectal cancer after a diagnosis of breast cancer. The association between breast cancer therapy and risk of colorectal cancer was evaluated in a subcohort of breast cancer patients treated in Stockholm between 1977 and 2007. Hazard ratios (HRs) and 95%CIs were estimated using Cox regression models.ResultsIn a cohort of 179,733 breast cancer patients in Sweden, 2571 incident cases of colorectal cancer (1008 adenocarcinomas in the proximal colon, 590 in the distal colon and 808 in the rectum) were identified during an average follow-up of 9.68 years. An increased risk of colorectal adenocarcinoma was observed in the breast cancer cohort compared with that in the general population (SIR=1.59, 95%CI: 1.53, 1.65). Adenocarcinoma in the proximal colon showed a non-significantly higher SIR (1.72, 95%CI: 1.61, 1.82) compared with the distal colon (1.46, 95%CI: 1.34, 1.58). In the subcohort of 20,171 breast cancers with available treatment data, 299 cases with colorectal cancers were identified. No treatment-dependent risk of colorectal cancer was observed among the breast cancer patients.ConclusionAn increased risk of colorectal adenocarcinoma - especially in the proximal colon - was observed in the breast cancer cohort. Breast cancer treatment did not alter this risk.

This research letter published in the British Journal of Surgery presents initial safety data from the PRORECT randomized trial, which compares the use of protons and photons in short-course radiotherapy for rectal cancer. The trial aims to determine if proton beam therapy (PBT) can reduce treatment-related toxicity compared to photon radiotherapy. The letter provides surgical outcomes for the first cohort of patients who underwent total neoadjuvant therapy with PBT or photon radiotherapy. The results suggest that PBT is as safe as photon-based radiotherapy from a surgical perspective, but further recruitment to the trial is encouraged due to the limited sample size. The document includes a table with various surgical details and outcomes of patients who underwent preoperative short-course radiation therapy for high-risk rectal cancer using protons compared to photons. The study is part of the ongoing PRORECT trial and aims to compare the dosimetric experience of proton therapy with photon therapy. The authors have disclosed no conflicts of interest and the data related to this report are available upon request. [Extracted from the article]

Background The incidence of colorectal cancer in patients aged less than 50 years is increasing in Western countries. This population‐based study investigated the age‐ and sex‐specific incidence of colorectal cancer over time in Sweden, and characterized trends in tumour localization and stage at diagnosis. Methods Patients diagnosed with colorectal cancer between 1970 and 2016 were identified from the Swedish Cancer Registry, and categorized by sex, age and tumour location. The incidence and average annual percentage change (AAPC) were estimated and compared between age groups. Results There was an overall increase in the incidence of colorectal cancer between 1970 and 2006, but a decrease in 2006–2016 (AAPC −0·55 (95 per cent c.i. −1·02 to −0·07) per cent). The largest increase in colonic cancer was in 1995–2005 in women aged less than 50 years (AAPC 2·30 (0·09 to 4·56) per cent versus 0·04 (−1·35 to 1·44) and − 0·67 (−1·62 to 0·28) per cent in women aged 50–74 and 75 years or more respectively). Since 1990, rectal cancer increased in patients of both sexes aged below 50 years, with higher AAPC values in women (2006–2016: 2·01 (−1·46 to 5·61) per cent versus 0·20 (−2·25 to 2·71) per cent in men). Younger patients were more likely than those aged 50–74 and 75 years or more to present with stage III–IV colonic (66·2, 57·6 and 49·6 per cent respectively) and rectal (61·2, 54·3 and 51·3 per cent) cancer. From the mid 1990s, rates of proximal and distal colorectal cancer, and rectal cancer were increased in patients aged less than 50 years. Conclusion The overall incidence of colorectal cancer in Sweden decreased in the past decade. However, in patients under 50 years of age the incidence of colorectal cancer – proximal, distal and rectal – continued to increase over time.

BackgroundSex hormones may be associated with colorectal adenocarcinoma, although the association of pregnancy history and risk of colorectal cancer is not consistent.MethodsWe conducted a population-based nested case-control study of persons born between 1932 and 2008 who are in the Swedish Multi-Generation Register. In total, 12,915 women and 15,519 men with colorectal adenocarcinoma were identified during follow-up in the Swedish Cancer Register; 10 age- and sex-matched controls were selected for each case. Number of children and age at first and last birth were analyzed in relation to the risk of colorectal adenocarcinoma, using conditional logistic regression, to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsCompared with women without children, women with 1 or 2 children had an OR of 1.02 (95% CI = 0.93-1.13) of developing adenocarcinoma in the proximal colon; those with 3 or 4 children, 1.18 (1.06-1.32); and those with ≥5 children, 1.30 (1.05-1.61) (test for trend P < 0.01). The corresponding associations in men were 0.92 (0.84-1.00), 1.02 (0.92-1.13), and 0.97 (0.78-1.20), respectively (test for trend P = 0.13).ConclusionsHigher parity in women was associated with the risk of adenocarcinoma of the proximal colon, although not the distal colon or rectum. A similar risk with family size was not seen for fathers. Still, the influence of lifestyle factors cannot be ruled out.

Simple Summary: In recent years, there have been significant improvements in the treatment of rectal cancer. Preoperative treatment and surgical techniques have advanced, leading to fewer local recurrences, fewer surgical complications, and more complete resections. Recent trials investigating total neoadjuvant treatment aim to decrease distant metastasis and improve overall survival in patients with locally advanced rectal cancer. In addition, adding chemotherapy to the preoperative treatment increases the complete response rate to 30 to 50 percent of patients. This means that no residual tumour is left and that patients can follow a Watch & Wait surveillance program, potentially avoiding surgery, complications, and colostomy. Nonetheless, many factors have to be considered when deciding on a treatment plan for patients with rectal cancer. Ongoing research aims to identify the optimal treatment regimen, considering factors like tumour stage, toxicity of (neo)adjuvant treatment, and patient preference. Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program. [ABSTRACT FROM AUTHOR]

Background This population‐based cohort study aimed to evaluate occurrence of low anterior resection syndrome (LARS) and correlate this to health‐related quality of life in patients who had undergone segmental colonic resection for colonic cancer in the Stockholm–Gotland region. The hypothesis was that there is a difference in occurrence of LARS depending on whether a right‐ or a left‐sided resection was performed. Methods Patients who underwent segmental colonic resection for colonic cancer stages I–III in the Stockholm–Gotland region in 2013–2015 received EORTC QLQ‐C30, QLQ‐CR29 and LARS score questionnaires 1 year after surgery. Clinical patient and tumour data were collected from the Swedish ColoRectal Cancer Registry. Patient‐reported outcome measures were analysed in relation to type of colonic resection. Results Questionnaires were sent to 866 patients and complete responses were provided by 517 (59·7 per cent). After right‐sided resection 20·6 per cent reported major LARS. After left‐sided resection the proportion with major LARS was 15·6 per cent. The odds ratio (OR) for major LARS after right‐sided resection was 1·45 (95 per cent c.i. 1·02 to 2·06; P = 0·037) compared with left‐sided resection. After adjustment for age and sex, an increase in the risk of major LARS after right‐ versus left‐sided resection remained (OR 1·48, 1·03 to 2·13; P = 0·035). Major LARS correlated with impaired quality of life. Conclusion Major LARS was more frequent after right‐sided than following left‐sided colonic resection. Major LARS reflected impaired quality of life.