Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae?

AIM: Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. METHOD: CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. RESULTS: A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. CONCLUSION: From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms.

Chronic loose stools following right-sided hemicolectomy for colon cancer and the association with bile acid malabsorption and small intestinal bacterial overgrowth.

AIM: Patients treated with right-sided hemicolectomy for colon cancer may suffer from long-term bowel dysfunction, including loose stools, urgency and faecal incontinence. The underlying causes are poorly understood. The aim of this case-control study was to investigate the aetiology of chronic loose stools among patients with right-sided hemicolectomy curatively operated for cancer. METHOD: Cases with chronic loose stools (Bristol stool type 6-7) after right-sided hemicolectomy were compared with a control group of patients with right-sided hemicolectomy without loose stools. All patients underwent a selenium-75 homocholic acid taurine (SeHCAT) scan to diagnose bile acid malabsorption (BAM) and a glucose breath test to diagnose small intestinal bacterial overgrowth (SIBO). Gastrointestinal transit time (GITT) was assessed with radiopaque markers. In a subgroup of patients, fibroblast growth factor 19 (FGF19) was measured in fasting blood. SIBO was treated with antibiotics and BAM was treated with bile acid sequestrants. RESULTS: We included 45 cases and 19 controls. In the case group, 82% (n = 36) had BAM compared with 37% (n = 7) in the control group, p < 0.001. SIBO was diagnosed in 73% (n = 33) of cases with chronic loose stools and in 74% (n = 14) of controls, p = 0.977. No association between BAM and SIBO was observed. GITT was similar in cases and controls. No difference in median FGF19 was observed between cases and controls (p = 0.894), and no correlation was seen between FGF19 and SeHCAT retention (rs 0.20, p = 0.294). Bowel symptoms among cases were reduced after treatment. CONCLUSION: BAM and SIBO are common in patients having undergone right-sided hemicolectomy for cancer. Chronic loose stools were associated with BAM but not with SIBO.

Management of treatment-related sequelae following colorectal cancer.

AIM: Colorectal cancer survivors are one of the most rapidly growing groups of patients living with and beyond cancer. In a national multidisciplinary setting, we have examined the extent of late treatment-related sequelae in colorectal cancer survivors and present the scientific evidence for management of these conditions in this patient category with the aim of facilitating identification and treatment. METHOD: A systematic search for existing guidelines and relevant studies was performed across 16 and 4 databases, respectively, from inception to 2021. This yielded 13 guidelines and 886 abstracts, of which 188 were included in the finalized guideline (231 included for full text review). Secondarily, bibliographies were cross-referenced and 53 additional articles were included. RESULTS: Symptoms have been divided into overall categories including psychosocial, bowel-related, urinary, sexual (male and female), pain/neuropathy and fatigue symptoms or complaints that are examined individually. Merging and grading of data resulted in 22 recommendations and 42 management strategies across categories. Recommendations are of a more general character, whereas management strategies provide more practical advice suited for initiation on site before referral to specialized units. CONCLUSION: Treatment-related sequelae in colorectal cancer survivors are common and attention needs to be focused on identifying patients with unmet treatment needs and the development of evidence-based treatment algorithms.

Implementation of a standardized surgical technique in robot-assisted restorative rectal cancer resection: a single center cohort study.

BACKGROUND: Despite increasing focus on the technical performance of total mesorectal excision over recent decades, anastomotic leakage (AL) continues to be a serious complication for many patients, even in the hands of experienced surgical teams. This study describes implementation of standardized surgical technique in an effort to reduce variability, decrease the risk of anastomotic leakage, and improve associated short-term outcomes for rectal cancer patients undergoing robot-assisted restorative rectal resection (RRR). METHODS: We evaluated all rectal cancer patients undergoing robot-assisted RRR at Aarhus University Hospital between 2017 and 2020. Six standardized surgical steps directed to improve anastomotic healing were mandatory for all RRR. Additional changes were made during the period with prohibition of systemic dexamethasone and limiting the use of endoscopic stapling devices. RESULTS: The use of the full standardization, including all six surgical steps, increased from 40.3% (95% CI, 0.28-0.54) to 86.2% (95% CI, 0.68-0.95). The incidence of AL decreased from 21.0% (95% CI, 0.12-0.33) to 6.9% (95% CI, 0.01-0.23). Length of hospital stay (LOS) decreased from 6 days (range 2-50) to 5 days (range 2-26). The rate of patients readmitted within 90 days decreased from 21.0% (95% CI, 0.12-0.33), to 6.9% (95% CI, 0.01-0.23). CONCLUSION: The full standardization was effectively implemented for rectal cancer patients undergoing robot-assisted RRR. The risk of AL, LOS and readmission decreased during the study period. A team focus on high-reliability and peri-operative complications can improve patient outcomes.

The impact of multiple firings on the risk of anastomotic leakage after minimally invasive restorative rectal cancer resection and the impact of anastomotic leakage on long-term survival: a population-based study.

PURPOSE: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival. METHODS: The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan-Meier methods and Cox regression. RESULTS: AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3-24.3) and 5.0% (95% CI 2.4-9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12-0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17-6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1-84.0) and 83.6% (95%CI 79.8-86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84-2.41). CONCLUSION: Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival.

Anastomotic leakage following restorative rectal cancer resection: treatment and impact on stoma presence 1 year after surgery-a population-based study.

PURPOSE: Anastomotic leakage (AL) continues to be a challenge after restorative rectal resection (RRR). Various treatment options of AL are available; however, their long-term outcomes are uncertain. We explored the impact of AL on the risk of stoma presence 1 year after RRR for rectal cancer and described treatment of AL after RRR including impact on the probability of receiving adjuvant chemotherapy and stoma presence following different treatment options of AL. METHODS: We included 859 patients undergoing RRR in Central Denmark Region between 2013 and 2019. Stoma presence was calculated as the proportion of patients with stoma 1 year after RRR. Multivariable logistic regression was conducted to estimate the impact of AL on stoma presence adjusting for potential predictors. Descriptive data of outcomes were stratified for various treatment options of AL. RESULTS: The risk of stoma presence 1 year after surgery was 9.8% (95% CI 7.98-12.0). Predictors for having stoma 1 year after RRR were AL (OR 8.43 (95% CI 4.87-14.59)) and low tumour height (OR 3.85 (95% CI 1.22-13.21)). For patients eligible for adjuvant chemotherapy, the probability of receiving it was 42.9% (95% CI 21.8-66.0) if treated with endo-SPONGE and 71.4% (95% CI 47.8-88.7) if treated with other anastomosis preserving treatment options. The risk of having stoma 1 year after RRR was 33.9% (95% CI 21.8-47.8) for patients treated with endo-SPONGE and 13.5% (95% CI 5.6-25.8) for patients treated with other anastomosis preserving treatment options (p = 0.013). CONCLUSION: AL is a strong predictor for stoma presence 1 year after RRR. Patients treated with endo-SPONGE seem to have worse outcomes compared to other anastomosis preserving treatment options.

Systematic screening for late sequelae after colorectal cancer-a feasibility study.

AIM: The aim of this study was to test the feasibility of a new method for systematic screening for late sequelae (LS) following colorectal cancer treatment. METHOD: Patients with colorectal cancer from five Danish hospitals were invited to complete a survey about LS at 3, 12, 24 and 36 months after surgery as part of their follow-up. The survey consisted primarily of validated tools, supplemented by a few ad hoc items, measuring bowel, urinary and sexual dysfunction, pain and quality of life and an additional question regarding request for contact. Patients completed surveys electronically or on paper. RESULTS: Of the 1721 invited patients, 1386 (80.5%) were included (1085 with colon cancer and 301 with rectal cancer) of whom 72.5% responded electronically. Patients responding electronically were 7.6 years younger than those responding on paper (P < 0.001). Since some patients answered more than once, the dataset consisted of 2361 surveys. Patients with colon cancer requested phone contact in 19.0% of the surveys, and 8.4% were referred to treatment for LS, primarily bowel dysfunction. Among patients with rectal cancer, 30.8% requested phone contact and 16.2% were referred for treatment of LS, mainly due to bowel and sexual dysfunction. CONCLUSION: This is the first paper investigating a new method of systematic screening for LS following colorectal cancer using electronic patient-reported outcome measures. The study shows that in the Danish population a high response rate can be obtained with this method and that close to three-quarters of patients respond electronically. Patients with rectal cancer had a higher need for phone contact and treatment of LS than patients with colon cancer.

Nurse-led standardized intervention for low anterior resection syndrome. A population-based pilot study.

AIM: Our aim was to study the implementation of the low anterior resection syndrome (LARS) score in a clinical setting and to evaluate a nurse-led standardized intervention for bowel dysfunction following rectal cancer surgery. METHOD: All patients who underwent curatively intended, restorative rectal cancer resection in a single centre between 2012 and 2016 were screened using the LARS score. At clinical follow-up, patients with major LARS were offered treatment in a nurse-led clinic. Data were retrospectively collected from patients' electronic medical records. RESULTS: In total, 190 out of 286 (66%) patients were screened with the LARS score of whom 89 had major LARS. A total of 86 patients requested treatment for their bowel dysfunction and the majority obtained acceptable function after nurse-led optimized conservative treatment. Seventeen patients went on to transanal irrigation, and seven patients were treated with biofeedback. Five patients were referred for surgery, three for gastroenterological evaluation. After treatment in the clinic, patients achieved a statistically significant decrease in median LARS score from 37 (interquartile range 34-39) to 31 (interquartile range 23-34) (P < 0.001), and the prevalence of major LARS fell from 95% to 53% (P < 0.001). CONCLUSION: Screening for LARS was not optimal as one-third of patients were not screened. The majority of patients with major LARS requested treatment for their symptoms and could be successfully treated with standardized interventions managed in a nurse-led setting.

Functional results after treatment for rectal cancer / Resultados funcionais após tratamento de câncer retal

INTRODUCTION: With improving survival of rectal cancer, functional outcome has become increasingly important. Following sphincter-preserving resection many patients suffer from severe bowel dysfunction with an impact on quality of life (QoL) - referred to as low anterior resection syndrome (LARS). STUDY OBJECTIVE: To provide an overview of the current knowledge of LARS regarding symptomatology, occurrence, risk factors, pathophysiology, evaluation instruments and treatment options. RESULTS: LARS is characterized by urgency, frequent bowel movements, emptying difficulties and incontinence, and occurs in up to 50-75% of patients on a long-term basis. Known risk factors are low anastomosis, use of radiotherapy, direct nerve injury and straight anastomosis. The pathophysiology seems to be multifactorial, with elements of anatomical, sensory and motility dysfunction. Use of validated instruments for evaluation of LARS is essential. Currently, there is a lack of evidence for treatment of LARS. Yet, transanal irrigation and sacral nerve stimulation are promising. CONCLUSION: LARS is a common problem following sphincter-preserving resection. All patients should be informed about the risk of LARS before surgery, and routinely be screened for LARS postoperatively. Patients with severe LARS should be offered treatment in order to improve QoL. Future focus should be on the possibilities of non-resectional treatment in order to prevent LARS. (AU)

INTRODUÇÃO: Com o aumento da sobrevida após câncer retal, o resultado funcional se tornou cada vez mais importante. Após ressecção com preservação do esfíncter, muitos pacientes sofrem de disfunção intestinal com um impacto sobre a qualidade de vida (QdV) - denominada síndrome da ressecção anterior baixa (LARS). OBJETIVO DO ESTUDO: Fornecer uma visão geral do conhecimento atual da LARS com relação à sintomatologia, à ocorrência, aos fatores de risco, à fisiopatologia, aos instrumentos de avaliação e às opções de tratamento. RESULTADOS: A LARS é caracterizada por movimentos intestinais repentinos e frequentes, dificuldades de esvaziamento e incontinência e ocorre em até 50-75% dos pacientes em longo prazo. Os fatores de risco conhecidos são anastomose baixa, radioterapia, lesão direta do nervo e anastomose direta. A fisiopatologia parece multifatorial, com elementos de disfunção anatômica, sensorial e da motilidade. O uso de instrumentos validados para avaliação da LARS é essencial. Atualmente, não há comprovações de tratamento da LARS. Ainda hoje, a irrigação transanal e a estimulação do nervo sacral são comprometidas. CONCLUSÃO: A LARS é um problema comum após ressecção com preservação do esfíncter. Todos os pacientes devem ser informados sobre o risco de LARS antes da cirurgia, e o rastreamento da LARS deve ser rotineiro após a cirurgia. Pacientes com LARS severa devem receber tratamento para melhorar a QdV. O foco futuro deve ser nas possibilidades de tratamento sem ressecção a fim de evitar a LARS. (AU)

Bowel dysfunction after rectal cancer treatment: a study comparing the specialist's versus patient's perspective.

OBJECTIVES: To investigate how bowel dysfunction after sphincter-preserving rectal cancer treatment, known as low anterior resection syndrome (LARS), is perceived by rectal cancer specialists, in relation to the patient's experience. DESIGN: Questionnaire study. SETTING: International. PARTICIPANTS: 58 rectal cancer specialists (45 colorectal surgeons and 13 radiation oncologists). RESEARCH PROCEDURE: The Low Anterior Resection Syndrome Score (LARS score) is a five-item instrument for evaluation of LARS, which was developed from and validated on 961 patients. The 58 specialists individually completed two LARS score-based exercises. In Exercise 1, they were asked to select, from a list of bowel dysfunction issues, five items that they considered to disturb patients the most. In Exercise 2, they were given a list of scores to assign to the LARS score items, according to the impact on quality of life (QOL). OUTCOME MEASURES: In Exercise 1, the frequency of selection of each issue, particularly the five items included in the LARS score, was compared with the frequency of being selected at random. In Exercise 2, the answers were compared with the original patient-derived scores. RESULTS: Four of the five LARS score issues had the highest frequencies of selection (urgency, clustering, incontinence for liquid stool and frequency of bowel movements), which were also higher than random. However, the remaining LARS score issue (incontinence for flatus) showed a lower frequency than random. Scores assigned by the specialists were significantly different from the patient-derived scores (p<0.01). The specialists grossly overestimated the impact of incontinence for liquid stool and frequent bowel movements on QOL, while they markedly underestimated the impact of clustering and urgency. The results did not differ between surgeons and oncologists. CONCLUSIONS: Rectal cancer specialists do not have a thorough understanding of which bowel dysfunction symptoms truly matter to the patient, nor how these symptoms affect QOL.

International validation of the low anterior resection syndrome score.

OBJECTIVE: The aims of this study were to investigate the convergent and discriminative validity and reliability of the low anterior resection syndrome (LARS) score in an international setting. BACKGROUND: The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal cancer surgery. The score is intended to be commonly used in international research and clinical practice in the future. Therefore, a thorough validation in an international setting is of utmost importance. METHODS: The LARS score was translated using methods in keeping with current international recommendations. A total of 801 patients operated for rectal cancer in Sweden, Spain, Germany, and Denmark completed the LARS score questionnaire, including an anchor question assessing the impact of bowel function on quality of life. A subgroup of 218 patients completed the LARS score twice. Data were analyzed per country. RESULTS: The LARS score has demonstrated a high convergent validity in terms of a high correlation between LARS score and quality of life (P < 0.001). Sensitivity ranged from 67.7% to 88.3% and specificity from 58.1% to 86.3%. The LARS score was able to discriminate between groups of patients differing with regard to radiotherapy, surgery, and age (P < 0.05). The score also demonstrated high reliability at test-retest with narrow limits of agreement and no statistically significant difference between scores at the first and second test. CONCLUSIONS: The Swedish, Spanish, German, and Danish versions of the LARS score have proven to be valid and reliable tools for measuring LARS in European rectal cancer patients.

Neorectal hyposensitivity after neoadjuvant therapy for rectal cancer.

BACKGROUND AND PURPOSE: Preoperative radiotherapy for rectal cancer has a detrimental effect on long-term anorectal function and quality of life, additional to that observed after rectal resection. The exact physiological mechanisms for the excess impairment remain unknown. We aimed to investigate neorectal and anal sphincter properties in patients treated with neoadjuvant therapy (NT) prior to total mesorectal excision (TME). MATERIAL AND METHODS: Sixteen patients (NT+ patients) were examined by multimodal neorectal stimulation and standard anorectal physiological testing. Data were compared to the results of 23 patients, who underwent TME without NT (NT- patients). RESULTS: NT+ patients had elevated sensory thresholds to heat (median temperature, 60 vs. 55 °C; p<0.01) and mechanical distension (median tension, 2513 vs. 1521 mmHg mm; p=0.05) in the fasting state, and altered perception of the sensory response to heat (p=0.01) and cold (p=0.01) compared to NT- patients. No differences in the biomechanical properties of the neorectal wall were detected. Anal resting pressure was lower in NT+ patients compared to NT- patients (median pressure, 31 vs. 45 cm H2O; p=0.05). CONCLUSIONS: Pelvic radiotherapy causes neorectal hyposensitivity to mechanical and thermal stimuli in patients receiving NT prior to TME surgery for rectal cancer, possibly due to impaired afferent nerve function.