Do beta-blockers reduce negative intrusive thoughts and anxiety in cancer survivors? - An emulated trial.

BACKGROUND: High rates of negative intrusive thoughts have been reported among cancer patients. Prevalent users of beta-blocker therapy have reported lower levels of cancer related intrusive thoughts than non-user. The aim of this study is to investigate if initiation of beta-blocker therapy reduces the prevalence and severity of intrusive thoughts (co-primary endpoints) and the prevalence of anxiety, depressed mood, and low quality of life (secondary endpoints) in cancer survivors. METHODS: Data on patient-reported outcomes from three cohort studies of Swedish patients diagnosed with colon, prostate or rectal cancer were combined with data on beta-blocker prescriptions retrieved from the Swedish Prescribed Drug Register. Two randomized controlled trials were emulated. Trial 1 had follow-up 1 year after diagnosis, trial 2 had follow-up 2 years after diagnosis, baseline in both trials was 12 months before follow-up. Those who initiated beta-blocker therapy between baseline and follow-up was assigned Active group, those who did not was assigned Control group. All endpoints were analysed using Bayesian ordered logistic regression. RESULTS: Trial 1 consisted of Active group, n = 59, and Control group, n = 3936. Trial 2 consisted of Active group, n = 87, and Control group, n = 3132. The majority of participants were men, 83% in trial 1 and 94% in trial 2. The prevalence and severity of intrusive thoughts were lower in the Active group in trial 1, but no significant differences between groups were found in either trial. The prevalence of depressed mood, worse quality of life and periods of anxiety were higher in the Active group in both trials with significant differences for quality of life in trial 1 and anxiety in trial 2. CONCLUSIONS: The emulated trials demonstrated no evidence of a protective effect of beta-blocker therapy against intrusive thoughts. The Active group had reduced quality of life and elevated anxiety compared to the Control group. TRIAL REGISTRATION: The three cohort studies were registered at isrctn.com/clinicaltrials.gov (ISRCTN06393679, NCT02530593 and NCT01477229).

Bowel Dysfunction After Colon Cancer Surgery: A Prospective, Longitudinal, Multicenter Study.

BACKGROUND: Longitudinal studies on functional outcome after colon resection are limited. OBJECTIVE: Examine bowel dysfunction and related distress one and three years after colon resection utilizing the low anterior resection syndrome score as well as specific validated items. DESIGN: This study presents the long-term results of bowel dysfunction and related distress based on the quality of life in colon cancer study, an observational, prospective multicenter study of patients with newly diagnosed colon cancer. SETTINGS: The study was conducted at 21 Swedish and Danish surgical centers between 2015 and 2019. PATIENTS: All patients who underwent right- or left-sided colon resection were considered eligible. Exclusion criteria were age below 18, cognitive impairment or inability to understand Swedish/Danish. Patients completed extensive questionnaires at diagnosis, and after one and three years. Clinical data were supplemented by national quality registries. MAIN OUTCOME MEASURES: The low anterior resection syndrome score, specific bowel symptoms and the patient-reported distress were assessed. RESULTS: Of 1,221 patients (83% response rate), 17% reported major LARS one year after either type of resection, consistent at 3 years (17% right, 16% left). In the long-term, the only significant difference between types of resection was a high occurrence of loose stools following right-sided resections. Overall, less than one-fifth of patients experienced distress, with women reporting more frequent symptoms and greater distress. In particular, incontinence and loose stools correlated strongly with distress. LIMITATIONS: Absence of pre-diagnosis bowel function data. CONCLUSIONS: Our study indicates that bowel function remains largely intact following colon resection, with only a minority reporting significant distress. Adverse outcomes were more common among women. The occurrence of loose stools following right-sided resection and the association between incontinence, loose stools, and distress highlights a need for postoperative evaluations and more thorough assessments beyond the LARS score when evaluating colon cancer patients. See Video Abstract.

Developing a multivariable prediction model of global health-related quality of life in patients treated for rectal cancer: a prospective study in five countries.

PURPOSE: Rectal cancer and its treatment have a negative impact on health-related quality of life (HRQoL). If risk factors for sustained low HRQoL could be identified early, ideally before the start of treatment, individualised interventions could be identified and implemented to maintain or improve HRQoL. The study aimed to develop a multivariable prediction model for global HRQoL 12 months after rectal cancer treatment. METHODS: Within COLOR II, a randomised, multicentre, international trial of laparoscopic and open surgery for rectal cancer, a sub-study on HRQoL included 385 patients in 12 hospitals and five countries. The HRQoL study was optional for hospitals in the COLOR II trial. EORTC QLQ-C30 and EORTC QLQ-CR38 were analysed preoperatively and at 1 and 12 months postoperatively. In exploratory analyses, correlations between age, sex, fatigue, pain, ASA classification, complications, and symptoms after surgery to HRQoL were studied. Bivariate initial analyses were followed by multivariate regression models. RESULTS: Patient characteristics and clinical factors explained 4-10% of the variation in global HRQoL. The patient-reported outcomes from EORTC QLQ-C30 explained 55-65% of the variation in global HRQoL. The predominant predictors were fatigue and pain, which significantly impacted global HRQoL at all time points measured. CONCLUSION: We found that fatigue and pain were two significant factors associated with posttreatment global HRQoL in patients treated for rectal cancer T1-T3 Nx. Interventions to reduce fatigue and pain could enhance global HRQoL after rectal cancer treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov No. NCT00297791.

Minor impact of anastomotic leakage in anterior resection for rectal cancer on long-term male urinary and sexual function.

PURPOSE: Anastomotic leakage after anterior resection for rectal cancer induces bowel dysfunction, but the influence on urinary and sexual function is largely unknown. This cross-sectional cohort study evaluated long-term effect of anastomotic leakage on urinary and sexual function in male patients. METHODS: Patients operated with anterior resection for rectal cancer in 15 Swedish hospitals 2007-2013 were identified. Anastomotic leakage and other clinical variables were retrieved from the Swedish Colorectal Cancer Registry and medical records. Urinary and sexual dysfunction were evaluated at 4 to 11 years after surgery using the International Prostate Symptom Score, International Index of Erectile Function, and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire CR29. The effect of anastomotic leakage on average scores of urinary and sexual dysfunction was evaluated as a primary outcome, and the single items permanent urinary catheter and sexual inactivity as secondary outcomes. The association of anastomotic leakage and functional outcomes was analyzed using regression models with adjustment for confounders. RESULTS: After a median follow-up of 84 months (interquartile range: 67-110), 379 out of 864 eligible men were included. Fifty-nine (16%) patients had anastomotic leakage. Urinary incontinence was more common in the leakage group, with an adjusted mean score difference measured by EORTC QLQ ColoRectal-29 of 8.69 (95% confidence interval: 0.72-16.67). The higher risks of urinary frequency, permanent urinary catheter, and sexual inactivity did not reach significance. CONCLUSION: Anastomotic leakage after anterior resection had a minor negative impact on urinary and sexual function in men.

Patient reported long-term side effects on bowel function and anal pain in anal cancer survivors - 3- and 6-year results from the Swedish national ANCA study.

AIM: The primary therapeutic option for anal cancer treatment is chemoradiotherapy resulting in 80% survival. The aim of this study was to assess long-term bowel function impairment and anal pain at 3 and 6 years after anal cancer diagnosis, based on a hypothesis of an increase in impairment over time. A secondary aim was to investigate if chemoradiotherapy increased the risk for bowel impairment, compared to radiotherapy alone. METHOD: The ANal CAncer study (ANCA) consists of a national Swedish cohort of patients diagnosed with anal cancer between 2011-2013. Patients within the study were invited to respond to a study-specific questionnaire at 3- and 6-years after diagnosis. Descriptive analyses for the primary endpoint and ordinal logistic regressions for secondary endpoint were performed. RESULTS: A total of 388 patients (84%) were included in the study. At 3 years of follow-up, 264 patients were alive. A total of 195 of these patients (74%) answered a study specific questionnaire, and at 6 years 154 patients (67%). Fifty-seven percent experienced bowel urgency at both 3 and 6 years. There was an increased risk for repeated bowel movement within 1 h (OR 2.44 [95% CI: 1.08-5.61, p = 0.03]) at 3 years in patients who had been treated by chemoradiation compared to radiotherapy alone. CONCLUSIONS: Impairment in bowel function and anal pain after anal cancer treatment should be expected and remains after 6 years. This suggests that long-term follow-up may be necessary in some form after customary follow-up. The addition of chemotherapy increases long-term side effects of bowel function.

Patient reported long-term side effects from treatment on urinary and sexual function in anal cancer survivors - 3- and 6-year results from the Swedish national ANCA study.

AIM: The standard treatment for anal cancer is chemoradiotherapy. Most patients survive anal cancer but remain living with long-term side effects related to the treatment received. The aim of this study was to assess the occurrence of long-term impairment of urinary and sexual function at 3 and 6 years after diagnosis and to investigate the additive effect from chemotherapy in combined chemoradiotherapy on urinary incontinence, compared to radiotherapy alone. METHOD: The ANal CAncer study (ANCA) is based on a national Swedish cohort of patients diagnosed with anal cancer between 2011 and 2013. All identified patients within the study were invited to respond to a study-specific questionnaire at 3 and 6 years. Descriptive analyses for the primary endpoint were performed. To investigate a possible additional effect from chemotherapy logistic regression was used. RESULTS: A total of 388 patients were included in the study. At 3 years 264 patients were alive and invited to respond to an anal cancer specific questionnaire. The 3- and 6 year response rates were 195 (74%) and 155 patients (67%), respectively. The patient reported urinary function impairment at 3 years were urgency (63%), incomplete bladder emptying (47%), and incontinence (46%) and there was an absolute increase of the prevalence of urinary dysfunction in about 10% at 6 years. Three years after diagnosis, 77% reported that intercourse was not part of their sex life; this percentage increased at 6 years to 83%. We found no negative effect of chemotherapy in combined chemoradiotherapy versus radiotherapy alone on patient reported urinary incontinence. CONCLUSION: For anal cancer survivors, urinary function was impaired after 3 years and continued to deteriorate as measured at 6 years after diagnosis. Anal cancer and its treatment negatively affected sexual function for both men and women. This may explain why patients reported that sexual activity and frequency of intercourse was not of importance in their life.

Suicide after colorectal cancer-a national population-based study.

AIM: A cancer diagnosis is often associated with physical as well as emotional distress. Previous studies indicate a higher risk for suicide in patients diagnosed with cancer. The aim of this study was to investigate the prevalence of death by suicide in a national cohort of patients with newly diagnosed colorectal cancer compared with a matched control group to determine if patients with colorectal cancer had an increased incidence of death by suicide. METHOD: This national Swedish cohort was retrieved from the register-based research database CRCBaSe, which includes all patients diagnosed with colorectal cancer between 1997-2006 (rectal) and 2008-2016 (colon) and six controls for each patient matched by age, sex, and county. Cause specific mortality due to suicide was modelled using Cox proportional hazards model and adjusted for known risk factors. RESULTS: The main analysis included patients operated for colorectal cancer, 55 578 patients compared with 307 888 controls. The first year after diagnosis the hazard ratio (HR) for suicide among patients operated for colorectal cancer was 1.86 (CI: 1.18-2.95) compared to controls. Suicide was more common among men than women (HR 2.08; 1.26-3.42 vs. 1.09; 0.32-3.75). A subgroup analysis of the 9198 patients who did not undergo surgery after diagnoses found a seven-fold increase of suicide (HR 7.03; 3.10-15.91). CONCLUSION: Suicide after surgery for colorectal cancer was almost twice as high as in the control group, mainly driven by excess mortality among men. Although the cases were few in the subgroup of nonoperated patients, the considerably higher risk of suicide indicates that more resources might be needed in this group. Evaluation of risk factors for suicide among patients with colorectal cancer should be performed for early identification of individuals at risk.

Long-term results of a short-term home-based pre- and postoperative exercise intervention on physical recovery after colorectal cancer surgery (PHYSSURG-C): a randomized clinical trial.

AIM: The aim of this work was to assess the effect of a short-term, home-based exercise intervention before and after colorectal cancer surgery on 12-month physical recovery within a previously reported randomized control trial (RCT). METHOD: PHYSSURG-C is an RCT in six participating hospitals in Sweden. Patients aged ≥20 years planned for elective colorectal cancer surgery were eligible. The intervention consisted of unsupervised moderate-intensity physical activity 2 weeks preoperatively and 4 weeks postoperatively. Usual care was control. The primary outcome measure in PHYSSURG-C was self-assessed physical recovery 4 weeks postoperatively. The predefined long-term follow-up outcomes included: self-assessed physical recovery 12 months postoperatively and reoperations and readmissions 91-365 days postoperatively. The statistical models were adjusted with tumour site (colon or rectum), neoadjuvant therapy (none, radiotherapy or chemo/radiotherapy) and type of surgery (open or laparoscopic). RESULTS: A total of 616 participants were available for the 12-month follow-up. Groups were balanced at baseline regarding demographic and treatment variables. There was no effect from the intervention on self-reported physical recovery [adjusted odds ratio (OR) 0.91, p = 0.60], the risk of reoperation (OR 0.97, p = 0.91) or readmission (OR 0.88, p = 0.58). CONCLUSION: The pre- and postoperative unsupervised moderate-intensity exercise intervention had no effect on long-term physical recovery after elective colorectal cancer surgery. There is still not enough evidence to support clinical guidelines on preoperative exercise to improve outcome after colorectal cancer surgery.

Mortality and morbidity after colorectal cancer resection surgery in elderly patients: a retrospective population-based study in Sweden.

BACKGROUND: Colorectal cancer is primarily a condition of older adults, and surgery is the cornerstone of treatment. As life expectancy is increasing and surgical techniques and perioperative care are developing, curative surgery is often conducted even in ageing populations. However, the risk of morbidity, functional decline, and mortality following colorectal cancer resection surgery are known to increase with increasing age. This study aims to describe real-world data about postoperative mortality and morbidity after resection surgery for colorectal cancer in the elderly (≥ 70 years) compared to younger patients (< 70 years), in a Swedish setting. METHODS: A cohort study including all patients diagnosed with colorectal cancer in a Swedish region of 1.7 million inhabitants between January 2016 and May 2020. Patients were identified through the Swedish Colorectal Cancer Registry, and all baseline and outcome variables were extracted from the registry. The following outcome measures were compared between the two age groups: 90-day mortality rates, postoperative complications, postoperative intensive care, reoperations, readmissions, and 1-year mortality. To adjust the analyses for baseline confounders in the comparison of the outcome variables, the following methods were used: marginal matching, calliper (ID matching), and logistic regression adjusted for baseline confounders. RESULTS: The cohort consisted of 5246 patients, of which 3849 (73%) underwent resection surgery. Patients that underwent resection surgery were significantly younger than those who did not (mean ± SD, 70.9 ± 11.4 years vs 73.7 ± 12.8 years, p < 0.001). Multivariable analyses revealed that both 90-day and 1-year mortality rates were higher in older patients that underwent resection surgery (90-day mortality OR 2.12 [95% CI 1.26-3.59], p < 0.005). However, there were no significant differences in postoperative intensive care, postoperative complications, reoperations, or readmissions. CONCLUSION: Elderly patients suffer increased postoperative mortality after resection surgery for colorectal cancer compared to younger individuals. Given the growing elderly population that will continue to require surgery for colorectal cancer, more efficient ways of determining and handling individual risk for older adults need to be implemented in clinical practice.

Short-term results in a population based study indicate advantage for minimally invasive rectal cancer surgery versus open.

BACKGROUND: The aim of this study was to determine if minimally invasive surgery (MIS) for rectal cancer is non-inferior to open surgery (OPEN) regarding adequacy of cancer resection in a population based setting. METHODS: All 9,464 patients diagnosed with rectal cancer 2012-2018 who underwent curative surgery were included from the Swedish Colorectal Cancer Registry. PRIMARY OUTCOMES: Positive circumferential resection margin (CRM < 1 mm) and positive resection margin (R1). Non-inferiority margins used were 2.4% and 4%. SECONDARY OUTCOMES: 30- and 90-day mortality, clinical anastomotic leak, re-operation < 30 days, 30- and 90-day re-admission, length of stay (LOS), distal resection margin < 1 mm and < 12 resected lymph nodes. Analyses were performed by intention-to-treat using unweighted and weighted multiple regression analyses. RESULTS: The CRM was positive in 3.8% of the MIS group and 5.4% of the OPEN group, risk difference -1.6% (95% CI -1.623, -1.622). R1 was recorded in 2.8% of patients in the MIS group and in 4.4% of patients in the OPEN group, risk difference -1.6% (95% CI -1.649, -1.633). There were no differences between the groups in adjusted unweighted and weighted analyses. All analyses demonstrated decreased mortality and re-admissions at 30 and 90 days as well as shorter LOS following MIS. CONCLUSIONS: In this population based setting MIS for rectal cancer was non-inferior to OPEN regarding adequacy of cancer resection with favorable short-term outcomes.

The impact of the anastomotic configuration on low anterior resection syndrome 3 years after total mesorectal excision for rectal cancer: a national cohort study.

AIM: After low anterior resection, the bowel can be anastomosed in different ways. It is not clear which configuration is optimal from a functional and complication point of view. The primary aim was to investigate the impact of the anastomotic configuration on bowel function evaluated by the low anterior resection syndrome (LARS) score. Secondarily, the impact on postoperative complications was evaluated. METHOD: All patients who had undergone low anterior resection from 2015 to 2017 were identified in the Swedish Colorectal Cancer Registry. Three years after surgery, patients were sent an extensive questionnaire and were analysed based on anastomotic configuration ('J-pouch/side-to-end anastomosis' or 'straight anastomosis'). Inverse probability weighting by propensity score was used to adjust for confounding factors. RESULTS: Among 892 patients, 574 (64%) responded, of whom 494 patients were analysed. After weighting, the anastomotic configuration had no significant impact on the LARS score (J-pouch/side-to-end OR 1.05, 95% confidence interval [CI] 0.82-1.34). The J-pouch/side-to-end anastomosis was significantly associated with overall postoperative complications (OR 1.43, 95% CI 1.06-1.95). No significant difference was seen regarding surgical complications (OR 1.14, 95% CI 0.78-1.66). CONCLUSION: This is the first study investigating the impact of the anastomotic configuration on long-term bowel function, evaluated by the LARS score, in an unselected national cohort. Our results suggested no benefit for J-pouch/side-to-end anastomosis on long-term bowel function and postoperative complication rates. The anastomotic strategy may be based upon the anatomical conditions of the patient and surgical preference.

Long-term oncological outcomes for minimally invasive surgery versus open surgery for colon cancer-a population-based nationwide study with a non-inferiority design.

AIM: The study aimed to compare 5-year overall survival in a national cohort of patients undergoing curative abdominal resection for colon cancer by minimally invasive surgery (MIS) or by the open (OPEN) technique. METHODS: All patients diagnosed between 2010 and 2016 in Sweden with pathological Union International Contre le Cancer Stages I-III colon cancer localized in the caecum, ascending colon, hepatic flexure or sigmoid colon and those who underwent curative right sided hemicolectomy, sigmoid resection or high anterior resection by MIS or OPEN were included. Patients were identified in the Swedish Colorectal Cancer Registry from which all data were retrieved. The analyses were performed as intention-to-treat and the relationship between surgical technique (MIS or OPEN) and overall mortality within 5 years was analysed. For the primary research question a non-inferiority hypothesis was assumed with a statistical power of 90%, a one-side type I error of 2.5% and a non-inferiority margin of 2%. For the secondary analyses, multilevel survival regression models with the patients matched by propensity scores were employed, adjusted for patient- and tumour-related variables. RESULTS: A total of 11 605 pathological Union International Contre le Cancer Stages I-III patients were included with 3297 MIS (28.4%) and 8308 OPEN (71.6%) and were followed until 31 December 2020. The primary analysis demonstrated superiority for MIS compared to OPEN. The multilevel survival regression analyses confirmed that 5-year overall survival was higher in MIS with a hazard ratio of 0.874 (95% confidence interval 0.791-0.965), and if excluding pT4 the outcome was similar, with a hazard ratio of 0.847 (95% confidence interval 0.756-0.948). CONCLUSION: This observational study demonstrated that MIS was favourable to OPEN with regard to 5-year overall survival. These results support the use of laparoscopic colon cancer surgery in routine practice.

Survival in relation to time to start of curative treatment of colon cancer: A national register-based observational noninferiority study.

AIM: There are ample discussions regarding the timing of treatment, especially in the era after Covid that caused delay to treatment. The aim of this study was to determine whether a delayed start to curative treatment, within 29-56 days after a diagnosis of colon cancer, was noninferior to starting treatment within 28 days, with regard to all-cause mortality. METHOD: This is a national register-based observational noninferiority study, with a noninferiority margin of hazard ratio (HR) 1.1, including all patients treated with curative intent for colon cancer in Sweden between 2008 and 2016. The primary outcome was all-cause mortality. Secondary outcomes were length of hospital stay, readmissions and reoperations within 1 year after surgery. Exclusion criteria were emergency surgery, disseminated disease at diagnosis, missing diagnosis date and treatment for another cancer 5 years before colon cancer diagnosis. RESULTS: A total of 20 836 individuals were included. A period of 29-56 days from diagnosis to start of curative treatment was noninferior versus starting treatment within 28 days for the primary outcome of all-cause mortality (HR 0.95, 95% CI 0.89-1.00). Starting treatment within 29-56 days was associated with a shorter length of stay (average 9.2 vs. 10 days) but a higher risk of reoperation compared to within 28 days. Post hoc analyses demonstrated that surgical modality was driving survival rather than time to treatment. Overall survival was greater after laparoscopic surgery (HR 0.78, 95% CI 0.69-0.88). CONCLUSION: For patients with colon cancer, a period of up to 56 days from diagnosis to the start of curative treatment did not lead to worse overall survival.

Functional Outcomes of Emergency Surgery for Perforated Diverticulitis, Hinchey Grade III.

BACKGROUND: Laparoscopic lavage as a treatment for perforated diverticulitis, Hinchey III, has been found safe and feasible in randomized trials. A few studies have reported functional outcomes and quality of life as secondary outcomes. This study investigated distress associated with dysfunction of the bowel or stoma, functional outcomes, and quality of life 2-3 years after surgery in a national unselected cohort. METHODS: All patients in Sweden who underwent emergency surgery for perforated diverticulitis with purulent peritonitis (2016-2018) were invited to answer a comprehensive, study-specific questionnaire 2-3 years after the index surgery. RESULTS: Out of 499 potential patients, 226 returned the questionnaire, and 209 were included in the analysis. There was no statistically significant difference between laparoscopic lavage and resection in distress associated with dysfunction of the bowel or stoma (odds ratio [OR], 1.32 [95% CI, 0.91-1.92]; p = 0.015). Bowel dysfunction measured by the LARS score was significantly higher for the lavage group (OR, 1.65 [95% CI, 1.11-2.45]), while stoma was more frequent after resection surgery (40 vs 6%). CONCLUSIONS: Patients experienced long-term distress from bodily dysfunction after emergency surgery for perforated diverticulitis regardless of the technique used. Regular follow-up could benefit these patients. TRIAL REGISTRATION: The project was registered at ClinicalTrials.gov on 2017-11-06. Identifier: NCT03332550. Acronym: LapLav.

Detection of magnetomotive ultrasound signals from human tissue.

Rectal cancer is a common cancer, with presently a 5-year survival of 67 %. Treatment is based on tumor stage, but current staging methods, such as magnetic resonance imaging (MRI) or ultrasound, are limited in the ability to correctly stage the disease. Magnetomotive ultrasound is a developing modality that has a potential to improve rectal cancer staging. Magnetic nanoparticles are set in motion by an external magnetic field, and the resulting motion signature is detected by ultrasound. Here, we report on magnetomotive images of magnetic nanoparticles in human tissue, using a prototype system where a rotating permanent magnet provides the varying magnetic field, and an ultrasound transducer array encircling the magnet, detects the induced motion. Prior to surgery, a patient with a low rectal tumor was injected at three sites close to the tumor with magnetic nanoparticles. Postsurgical magnetomotive ultrasound scanning revealed the three injection sites, with no obvious artefactual signals. A phantom study showed detection of nanoparticles beyond 40 mm, where 30 mm is the expected maximum distance to mesorectal lymph nodes. Magnetomotive ultrasound image of iron oxide nanoparticles in human tissue. Prior to surgery a patient was injected with nanoparticles, and the excised tissue specimen was imaged with a prototype magnetomotive ultrasound system. The three colored areas overlaid on the standard B-mode greyscale image, correspond to the three injection sites.

Effect of Short-term Homebased Pre- and Postoperative Exercise on Recovery After Colorectal Cancer Surgery (PHYSSURG-C): A Randomized Clinical Trial.

OBJECTIVE: To determine the effect of a short-term, unsupervised exercise intervention before and after colorectal cancer surgery on self-assessed physical recovery. SUMMARY OF BACKGROUND DATA: Preoperative exercise interventions could help improve recovery after colorectal cancer surgery and is currently recommended. METHODS: A randomized, parallel, open-label trial in six university or regional hospitals in Sweden. Inclusion criteria were age ≥20 years and planned elective colorectal cancer surgery. Participants were randomized to either a physical activity intervention with aerobic activity and inspiratory muscle training 2 weeks pre- and 4 weeks postoperatively or usual care. The primary outcome measure was self-assessed physical recovery 4 weeks postoperatively. Analyses were performed according to intention to treat. Outcome assessors were masked regarding the intervention while both participants and physiotherapists were informed due to the nature of the intervention. RESULTS: Between January 22, 2015, and May 28, 2020, 761 participants were recruited and assigned to either intervention (I) (n = 379) or control (C) (n = 382). After exclusions 668 participants (I = 317, C = 351) were included in the primary analysis. There was no effect from the intervention on the primary outcome measure (adjusted odds ratio 0.84, 95% confidence interval 0.62-1.15) with 13% and 15% of participants feeling fully physically recovered in I and C, respectively. There were no reported adverse events. CONCLUSIONS: There was no effect from a physical activity intervention before and after colorectal cancer surgery on short-term self-assessed physical recovery. The results from this study call for reconsiderations regarding current recommendations for preoperative physical activity interventions.

High Risk of Low Anterior Resection Syndrome in Long-term Follow-up After Anastomotic Leakage in Anterior Resection for Rectal Cancer.

BACKGROUND: Low anterior resection syndrome is common after sphincter-sparing surgery, but it is unclear to what extent anastomotic leakage after anterior resection contributes to this condition. OBJECTIVE: The aim of this study is to assess the long-term effect of anastomotic leakage on the occurrence of major low anterior resection syndrome. DESIGN: This is a retrospective observational cohort study evaluating low anterior resection syndrome 4 to 11 years after index surgery. After propensity score-matching using the covariates sex, age, tumor stage, comorbidity, neoadjuvant treatment, extent of mesorectal excision, and defunctioning stoma at index surgery, the effect of anastomotic leakage on low anterior resection syndrome was investigated using relative risk and 95% CI. SETTINGS: This multicenter study included patients from 15 Swedish hospitals between 2007 and 2013. PATIENTS: Patients who underwent anterior resection for rectal cancer were included. MAIN OUTCOME MEASURES: Outcome measures included patient-reported major low anterior resection syndrome, obtained via a postal questionnaire that included a question on stoma status. RESULTS: Among 1099 patients, 653 (59.4%) responded in at a median of 83.5 (interquartile range 66 to 110) months postoperatively. After excluding patients with residual stoma or incomplete responses, 544 remained; of these, 42 had anastomotic leakage. Patients with anastomotic leakage were more likely to have major low anterior resection syndrome (66.7% [28/42]) than patients without leakage (45.8% [230/502]). After matching, anastomotic leakage was significantly related to major low anterior resection syndrome (relative risk 2.3; 95% CI 1.4-3.9) and the individual symptom of urgency (relative risk 2.1; 95% CI 1.1-4.1). LIMITATIONS: This study was limited by its retrospective observational study design. CONCLUSIONS: In long-term follow-up, major low anterior resection syndrome is common after anterior resection for rectal cancer. Anastomotic leakage appears to increase the risk of major low anterior resection syndrome, with urgency as a major contributing symptom. See Video Abstract at http://links.lww.com/DCR/B868 . ALTO RIESGO DE SNDROME DE RESECCIN ANTERIOR BAJA EN EL SEGUIMIENTO A LARGO PLAZO TRAS FUGA ANASTOMTICA EN RESECCIN ANTERIOR POR CNCER DE RECTO: ANTECEDENTES:El síndrome de resección anterior baja es común después de una cirugía con preservación de esfínter pero no está claro hasta qué punto contribuye a esta condición la fuga anastomótica después de una resección anterior.OBJETIVO:El objetivo de este estudio es evaluar el efecto a largo plazo de la fuga anastomótica sobre la aparición de un síndrome de resección anterior baja mayor.DISEÑO:Se trata de un estudio de cohorte observacional retrospectivo que evalúa el síndrome de resección anterior baja 4-11 años después de la cirugía índice. Después del apareamiento por puntuación de propensión utilizando las covariables sexo, edad, estadio del tumor, comorbilidad, tratamiento neoadyuvante, extensión de la escisión mesorrectal y estoma de derivación en la cirugía índice, se investigó el efecto de la fuga anastomótica en el síndrome de resección anterior baja utilizando el riesgo relativo y intervalos de confianza de 95%.AJUSTES:Este estudio multicéntrico incluyó pacientes de 15 hospitales suecos entre 2007 y 2013.PACIENTES:Se incluyeron pacientes que fueron sometidos a resección anterior por cáncer de recto.PRINCIPALES MEDIDAS DE DESENLACE:Síndrome de resección anterior baja mayor informado por el paciente, obtenido a través de un cuestionario postal que incluye una pregunta sobre el estado de estomas.RESULTADOS:De 1099 pacientes, 653 (59,4%) respondieron una mediana de 83,5 meses después de la operación (rango intercuartílico 66-110).Después de excluir a los pacientes con estoma residual o respuestas incompletas, quedaron 544; de estos, 42 tuvieron fuga anastomótica. Los pacientes con fuga anastomótica tenían síndrome de resección anterior baja mayor en el 66,7% (28/42) en comparación con el 45,8% (230/502) de los pacientes sin fuga. Después del apareamiento, la fuga anastomótica se relacionó significativamente con el síndrome de resección anterior baja mayor (riesgo relativo 2,3; intervalo de confianza del 95%: 1,4-3,9) y con el síntoma individual de urgencia (riesgo relativo 2,1; intervalo de confianza del 95% 1,1-4,1).LIMITACIONES:Este estudio estuvo limitado por su diseño de estudio observacional retrospectivo.CONCLUSIONES:En el seguimiento a largo plazo, el síndrome de resección anterior baja mayor es común después de la resección anterior por cáncer de recto. La fuga anastomótica parece aumentar el riesgo de síndrome de resección anterior baja mayor, siendo la urgencia uno de los principales síntomas contribuyentes. Consulte Video Resumen en http://links.lww.com/DCR/B868 . (Traducción-Dr. Juan Carlos Reyes ).

Symptoms and diagnosis of local recurrence after rectal cancer treatment.

AIM: The prognosis for local recurrence after rectal cancer treatment is poor. A minority of patients are eligible for surgery with curative intent, which could possibly be improved by earlier detection. The aim of this study was to determine symptoms at presentation and how local recurrence was diagnosed, and to identify alarm symptoms for local recurrence as opposed to symptoms found among patients after surgery for rectal cancer in general. METHODS: In a population-based retrospective cohort (cohort A), all patients who had undergone resection surgery for rectal cancer in the region of Västra Götaland, Sweden, diagnosed 2010-2014, were identified through the Swedish ColoRectal Cancer Registry. After a follow-up period of at least five years, medical records were reviewed to identify patients diagnosed with local recurrence. Data on symptoms, diagnostic procedures and treatment of local recurrence were retrieved. A prospective cohort of patients who had undergone surgery for rectal cancer without local recurrence (the QoLiRECT-study, cohort B) was used for comparison regarding symptoms at two years after treatment. RESULTS: Cohort A consisted of 1208 patients, out of whom 78 (6%) were diagnosed with local recurrence. Forty-six patients were diagnosed between scheduled follow-up visits. Fifty-eight patients were symptomatic at the time of diagnosis, and the most common symptoms were pain, bleeding and urogenital symptoms. Pain was more common in patients with local recurrence when comparing cohort A with cohort B. CONCLUSION: A majority of patients with local recurrence were diagnosed outside of the scheduled follow-up. Most of the patients were symptomatic at diagnosis. Symptoms were common in patients after rectal cancer surgery in general, however pain was more common in patients with local recurrence and could represent an alarm symptom.

Long-term survival after treatment for primary anal cancer- results from the Swedish national ANCA cohort study.

BACKGROUND: Squamous cell carcinoma of the anus is increasing in incidence but remains a rare disease with good 3- and 5-year recurrence free and overall survival rates of 63%-86%. The treatment includes chemoradiotherapy, mainly with 5-fluoruracil (5FU) and mitomycin. The aim of this study was to describe long-term (up to 9 years after treatment) oncological outcome and the types of treatments given, in a Swedish national cohort of patients diagnosed with anal cancer between 2011 and 2013. METHOD: Patients were identified in the Swedish Cancer Registry. Patients still alive were contacted and asked for consent. Clinical data were retrieved from National Patient Register at the Swedish National Board of Health and Welfare and from medical records. Unadjusted and adjusted analyses were performed for overall survival. RESULTS: Three hundred and eighty-eight patients were included in the study of which 338 patients (87%) received treatment with a curative intent. Follow up was 85 months (0-113 months) for patients treated with curative intent (information missing in one patient) 7.5 months (0-55) for patients with treated with a palliative intent. Curative treatment varied and consisted of both chemoradiotherapy and radiotherapy (46-64 Gy) alone. 5-FU, mitomycin and cisplatin were the most used chemotherapy agents. Five-year overall survival for patients treated with curative intent was 73%. In an adjusted analysis 5-FU and mitomycin is associated with a lower mortality than 5-FU and cisplatin but the association was weaker (HR 1.61 (95% CI: 0.904; 2.85) than in the unadjusted analysis. CONCLUSIONS: In this national cohort overall five-year survival was 73% for patients treated with curative intent. As reported by others our results indicate that 5-FU and mitomycin C should be the preferred chemotherapy in treatment for cure.

Anal cancer in Sweden 2015-2019. Implementation of guidelines, structural changes, national registry and early results.

BACKGROUND: Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR). METHODS: The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015. RESULTS: The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%. CONCLUSIONS: This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.