Towards patient-led follow-up after curative surgical resection of stage I, II and III colorectal cancer (DISTANCE-trial): a study protocol for a stepped-wedge cluster-randomised trial.

BACKGROUND: Colorectal cancer (CRC) is among the most frequently diagnosed cancers. Approximately 20-30% of stage I-III CRC patients develop a recurrent tumour or metastases after curative surgical resection. Post-operative follow-up is indicated for the first five years after curative surgical resection. As intensified follow-up after curative surgical resection has shown no effect on survival, patient organisations and policy makers have advocated for a more patient-centred approach to follow-up. The objective of this study is to successfully implement patient-led, home-based follow-up (PHFU) in six hospitals in The Netherlands, with as ultimate aim to come to a recommendation for a patient-centred follow-up schedule for stage I-III CRC patients treated with surgical resection with curative intent. METHODS: This study is designed as a stepped-wedge cluster-randomised trial (SW-CRT) in six participating centres. During the trial, three centres will implement PHFU after six months; the other three centres will implement PHFU after 12 months of inclusion in the control group. Eligible patients are those with pT2-4N0M0 or pT1-4N1-2M0 CRC, who are 18 years or older and have been free of disease for 12 months after curative surgical resection. The studied intervention is PHFU, starting 12 months after curative resection. The in-hospital, standard-of-care follow-up currently implemented in the participating centres functions as the comparator. The proportion of patients who had contact with the hospital regarding CRC follow-up between 12-24 months after curative surgical resection is the primary endpoint of this study. Quality of life, fear of cancer recurrence, patient satisfaction, cost-effectiveness and survival are the secondary endpoints. DISCUSSION: The results of this study will provide evidence on whether nationwide implementation of PHFU for CRC in The Netherlands will be successful in reducing contact between patient and health care provider. Comparison of PROMs between in-hospital follow-up and PHFU will be provided. Moreover, the cost-effectiveness of PHFU will be assessed. TRIAL REGISTRATION: Dutch Trail Register (NTR): NL9266 (Registered on January 1st, 2021).

Delayed surgical resection of primary left-sided obstructing colon cancer is associated with improved short- and long-term outcomes.

BACKGROUND AND OBJECTIVES: It is unclear what time interval is optimal between presentation and surgical resection of left-sided obstructive colon cancer (LSOCC). This study aims to determine whether a time interval beyond 4 weeks is associated with a better outcome. MATERIALS AND METHODS: Consecutive patients who underwent surgical resection of LSOCC between January 2010 and December 2019 were collected from a prospective database. Patients were divided into three groups: (1) Emergency resection (ER group), (2) surgery in less than 4 weeks (early group), and (3) surgery beyond 4 weeks (late group). RESULTS: The ER group consisted of 74 (44.0%), the early group of 38 (22.6%), and the late group of 56 (33.3%) patients. Ninety-day mortality was lower in the Late group than in the ER group and the early group (1.8% vs. 12.2%, p = 0.029 vs. 15.3%, p = 0.011). In the late group 5-year recurrence-free survival was better than in the early group (82.1% vs. 63.2%, p = 0.039) and 5-year overall survival (OS) was better than in the ER group (75% vs. 51.4%, p = 0.021). Definitive surgical resection beyond 4 weeks was an independent prognostic factor for OS (Hazard ratio: 0.402, 95% CI: 0.204-0.793, p = 0.009). CONCLUSION: In this study surgical resection beyond 4 weeks after presentation seems to have a better short- and long-term outcome for LSOCC.

Implementation of robot-assisted total mesorectal excision by multiple surgeons in a large teaching hospital: Morbidity, long-term oncological and functional outcome.

BACKGROUND: Robot-assisted total mesorectal excision (TME) might offer benefits in less morbidity, better functional and long-term outcome over laparoscopic TME. METHODS: All consecutive patients undergoing robot-assisted TME for rectal cancer during implementation between May 2015 and December 2019 performed by five surgeons in a single centre were included. Outcomes included local recurrence rate at 3 years, conversion rate, circumferential resection margin (CRM) positivity rate, 30-day postoperative morbidity and outcomes of low anterior resection syndrome (LARS) questionnaires. RESULTS: In 105 robot-assisted TME, local recurrence rate at 3 years was 7.4%, conversion to open surgery rate was 8.6%, CRM positivity rate was 5.7%, 73.3% had good quality specimen, postoperative morbidity rate was 47.6% and anastomotic leakage rate was 9.0%. Incidence of major LARS was 55.3%. CONCLUSIONS: results of this study described acceptable morbidity, functional and long-term outcome during implementation of robotic TME for rectal cancer by multiple surgeons in a single centre.

Oncological outcomes of unsuspected pN2 in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Optimal treatment of stage IIIA (N2) non-small-cell lung cancer (NSCLC) is controversial. Guidelines advise induction therapy before surgical resection. A proportion of patients with cN0 NSCLC are postoperatively upstaged due to unsuspected N2 disease. Survival of unsuspected N2 NSCLC treated with surgery varies and technical feasibility of video-assisted thoracic surgery (VATS) is unknown. The purpose of this study was to assess prevalence and survival of unsuspected N2 NSCLC treated with thoracotomy or VATS. METHODS: A systematic review and meta-analysis was performed of all available literatures through Pubmed, Cochrane, EMBASE, Web of Science, Trials registries and System for Information on Grey Literature (SIGLE) from 2000 to 2019. Outcomes of interest were prevalence, overall survival (OS) and disease-free survival of unsuspected N2 NSCLC. Secondary outcomes were number of harvested lymph nodes, postoperative complications and survival of unsuspected N2 NSCLC treated with VATS. RESULTS: Seventeen studies with patients with clinical stage N0-1 and unsuspected pN2 NSCLC were included. Prevalence of unsuspected pN2 was 8.6%. Three- and 5-year OS was 58% [95% confidence interval (CI) 37-78%) (N = 4337] and 35% (95% CI 28-43%) (N = 4337). Three- and 5-y ear disease-free survival was 48% (95% CI 30-66%) (N = 109) and 35% (95% CI 24-46%) (N = 517). VATS resulted in a low complication rate with similar 5-year OS as thoracotomy. CONCLUSIONS: In patients with cN0-1 NSCLC, a minority has unsuspected pN2 NSCLC. Even for these patients, 5-year OS and disease-free survival are reasonable. VATS with adequate lymph node dissection is the treatment of choice when in experienced hands. Adjuvant therapy should be provided in absence of relevant comorbidity.

The impact of postoperative complications on health-related quality of life in older patients with rectal cancer; a prospective cohort study.

OBJECTIVES: As result of the aging population and increasing rectal cancer incidence, more older patients undergo treatment for rectal cancer. This study compares treatment course, postoperative complications, and quality of life (QOL) between older and younger patients with rectal cancer and evaluates the impact of postoperative complications on QOL in the elderly. MATERIALS AND METHODS: Patients with rectal cancer participating in a prospective colorectal cancer cohort and referred for radiotherapy between 2013 and 2016 were included. QOL was assessed with the cancer questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) before treatment and at three, six, and twelve months. Outcomes were compared between older patients (≥70years) and younger patients (<70years) and stratified by presence of postoperative complications. RESULTS: In total, 115 (33%) older patients and 230 (67%) younger patients were included. Compared to younger patients, older patients underwent significantly more often short-course radiation with delayed surgery (6.1% and 19.1% respectively) and less often chemoradiation (62.6% and 39.1% respectively), and were more likely to undergo a Hartmann procedure with permanent stoma (3.5% and 13.0% respectively) instead of sphincter-sparing surgery (43.9% and 29.6% respectively). Postoperative complication rates were similar (38.5% in older patients versus 34.7% in younger patients). Older patients had worse physical functioning at six and twelve months after diagnosis compared to younger patients. Presence of postoperative complications had a significant stronger impact on physical- and role functioning in older patients. CONCLUSION: Older patients undergo more often a tailored treatment approach for rectal cancer than younger patients. With this tailored approach, similar postoperative complication rates and QOL are achieved. However, postoperative complications have a larger negative impact on physical- and role functioning in older patients which indicates a need for better prediction of postoperative complications in the elderly.

Cost-effectiveness analysis of an 18-week exercise programme for patients with breast and colon cancer undergoing adjuvant chemotherapy: the randomised PACT study.

OBJECTIVE: Meta-analyses show that exercise interventions during cancer treatment reduce cancer-related fatigue. However, little is known about the cost-effectiveness of such interventions. Here we aim to assess the cost-effectiveness of the 18-week physical activity during cancer treatment (PACT) intervention for patients with breast and colon cancer. The PACT trial showed beneficial effects for fatigue and physical fitness. DESIGN: Cost-effectiveness analyses with a 9-month time horizon (18 weeks of intervention and 18 weeks of follow-up) within the randomised controlled multicentre PACT study. SETTING: Outpatient clinics of 7 hospitals in the Netherlands (1 academic and 6 general hospitals) PARTICIPANTS: 204 patients with breast cancer and 33 with colon cancer undergoing adjuvant treatment including chemotherapy. INTERVENTION: Supervised 1-hour aerobic and resistance exercise (twice per week for 18 weeks) or usual care. MAIN OUTCOME MEASURES: Costs, quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio. RESULTS: For colon cancer, the cost-effectiveness analysis showed beneficial effects of the exercise intervention with incremental costs savings of €4321 and QALY improvements of 0.03. 100% of bootstrap simulations indicated that the intervention is dominant (ie, cheaper and more effective). For breast cancer, the results did not indicate that the exercise intervention was cost-effective. Incremental costs were €2912, and the incremental effect was 0.01 QALY. At a Dutch threshold value of €20 000 per QALY, the probability that the intervention is cost-effective was 2%. CONCLUSIONS: Our results suggest that the 18-week exercise programme was cost-effective for colon cancer, but not for breast cancer. TRIAL REGISTRATION NUMBER: ISRCTN43801571.

Quality of Life After a Low Anterior Resection for Rectal Cancer in Elderly Patients.

PURPOSE: Fecal incontinence is a major concern, and its incidence increases with age. Quality of life may decrease due to fecal incontinence after both sphincter-saving surgery and a rectal resection with a permanent stoma. This study investigated quality of life, with regard to fecal incontinency, in elderly patients after rectal-cancer surgery. METHODS: All patients who underwent elective rectal surgery with anastomosis for rectal cancer between December 2008 and June 2012 at two Dutch hospitals were eligible for inclusion. The Wexner and the fecal incontinence quality of life (FIQoL) scores were collected. Young (<70 years of age) and elderly (≥70 years of age) patients were compared. RESULTS: Seventy-nine patients were included, of whom 19 were elderly patients (24.1%). All diverting stomas that had been placed (n = 60, 75.9%) had been closed at the time of the study. There were no differences in Wexner or FIQoL scores between the young and the elderly patients. Also, there were no differences between patients without a diverting stoma and patients in whom bowel continuity had been restored. Elderly females had significantly worse scores on the FIQoL subscales of coping/behavior (P = 0.043) and depression/self-perception (P = 0.004) than young females. Elderly females scored worse on coping/behavior (P = 0.010) and depression/self-perception (P = 0.036) than elderly males. Young and elderly males had comparable scores. CONCLUSION: Quality of life with regard to fecal incontinency is worse in elderly females after sphincter-preserving surgery for rectal cancer. Patients should be informed of this impact, and a definite stoma may be considered in this patient group.

Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy.

PURPOSE: Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted. METHODS: In this multicenter randomized controlled trial, 33 colon cancer patients undergoing chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk. RESULTS: Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group. CONCLUSION: The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required.

Erratum.

[This corrects the article on p. 23 in vol. 31, PMID: 25745623.].

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial.

BACKGROUND: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. METHODS: This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. RESULTS: Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. CONCLUSIONS: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43801571, Dutch Trial Register NTR2138. Trial registered on December 9th, 2009.

Predictors of fecal incontinence and related quality of life after a total mesorectal excision with primary anastomosis for patients with rectal cancer.

PURPOSE: After total mesorectal excision (TME) with primary anastomosis for patients with rectal cancer, the quality of life (QoL) may be decreased due to fecal incontinence. This study aimed to identify predictors of fecal incontinence and related QoL. METHODS: Patients who underwent TME with primary anastomosis for rectal cancer between December 2008 and June 2012 completed the fecal incontinence quality of life scale (FIQoL) and Wexner incontinence score. Factors associated with these scores were identified using a linear regression analysis. RESULTS: A total of 80 patients were included. Multivariate analysis identified a diverting ileostomy (n = 58) as an independent predictor of an unfavorable outcome on the FIQoL subscale coping/behavior (P = 0.041). Ileostomy closure within and after 3 months resulted in median Wexner scores of 5.0 (interquartile range [IQR], 2.5-8.0) and 10.5 (IQR, 6.0-13.8), respectively (P < 0.001). The median FIQoL score was 15.0 (IQR, 13.1-16.0) for stoma closure within 3 months versus 12.0 (IQR, 10.5-13.9) for closure after 3 months (P = 0.001). CONCLUSION: A diverting ileostomy is a predictor for an impaired FIQoL after a TME for rectal cancer. Stoma reversal within 3 months showed better outcomes than reversal after 3 months. Patients with a diverting ileostomy should be informed about the impaired QoL, even after stoma closure.

Breast cancer surgery without drains: no influence on seroma formation.

It is not clear whether drains are necessary after breast cancer surgery. The purpose of this study was to compare seroma formation in patients that had postoperative drainage for 24 h with patients that had no drain after breast cancer surgery. In this retrospective cohort study 96 patients with a primary breast cancer were included. Between January 2009 and April 2011 44 patients had breast cancer surgery followed by postoperative drainage. Between May 2011 and February 2013 52 patients underwent breast cancer surgery without drainage. The operative procedures that were included were: axillary lymph node dissection, modified radical mastectomy or simple mastectomy±sentinel lymph node biopsy. There was no difference between both groups regarding frequency of seroma (84.6% versus 90.9%; p=0.290) and amount of seroma (540 ml versus 590 ml; p=0.446). Postoperative hospital stay was shorter in patients without drainage (2 versus 2.5 days; p=0.003). There was no difference between both groups in other secondary outcome measures. Modified radical mastectomy was an independent predictor of the amount of postoperative seroma (HR 0.039 [0.007-0.235]; p<0.001). These results suggest that there is no difference in seroma after breast cancer surgery between patients that had postoperative drainage and patients that had no postoperative drainage.

Aggressiveness of 'true' interval invasive ductal carcinomas of the breast in postmenopausal women.

There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between 'true' interval carcinomas and screen-detected/missed carcinomas hypothesising that 'true' interval carcinomas show a more aggressive biological behaviour. The study group consisted of 92 consecutive postmenopausal women attending the breast screening programme and presenting with an invasive ductal carcinoma. All screening mammograms were re-reviewed. Sixteen patients had a 'true' interval carcinoma. Seven carcinomas were missed at screening, but detected on re-reviewing of the screening mammogram. Radiological characteristics were assessed from diagnostic mammograms. Data on patient- and tumour characteristics and follow-up data were recorded from hospital records. Median follow-up was 61 months. Immunohistochemistry for ER, PR, Her2/neu and p53 was performed on TMA sections. Univariate and multivariate logistic regression analyses were performed. In univariate analysis, 'true' interval carcinomas were significantly larger (odd ratios (OR) 7.2, 95% CI 1.8-28.1) and less frequently ER (OR 0.3, 95% CI 0.1-0.9) and PR (OR 0.3, 95% CI 0.1-1.0) positive. In multivariate analysis, 'true' interval carcinoma was independently associated with larger tumours (OR 7.0, 95% CI 1.4-36.2). A trend toward ER negativity was found (OR 0.3, 95% CI 0.1-1.1). 'True' interval carcinomas showed a trend toward a decreased relapse-free survival (HR 1.7 95% CI 0.9-3.1). Although 'true' interval carcinomas were significantly larger than screen-detected/missed interval carcinomas, it remains challenging to observe parameters that determine this difference between 'true' interval carcinomas and screen-detected lesions.

Correlation between imaging and pathology in ductal carcinoma in situ of the breast.

BACKGROUND: It is helpful in planning treatment for patients with ductal carcinoma in situ (DCIS) if the size and grade could be reliably predicted from the mammography. The aims of this study were to determine if the type of calcification can be best used to predict histopathological grade from the mammograms, to examine the association of mammographic appearance of DCIS with grade and to assess the correlation between mammographic size and pathological size. METHODS: Mammographic films and pathological slides of 115 patients treated for DCIS between 1986 and 2000 were reviewed and reclassified by a single radiologist and a single pathologist respectively. Prediction models for the European Pathologist Working Group (EPWG) and Van Nuys classifications were generated by ordinal regression. The association between mammographic appearance and grade was tested with the chi2-test. Relation of mammographic size with pathological size was established using linear regression. The relation was expressed by the correlation coefficient (r). RESULTS: The EPWG classification was correctly predicted in 68%, and the Van Nuys classification in 70% if DCIS was presented as microcalcifications. High grade was associated with presence of linear calcifications (p < 0.001). Association between mammograhic- and pathological size was better for DCIS presented as microcalcifications (r = 0.89, p < 0.001) than for DCIS presented as a density (r = 0.77, p < 0.001). CONCLUSIONS: Prediction of histopathological grade of DCIS presenting as microcalcifications is comparable using the Van Nuys and EPWG classification. There is no strict association of mammographic appearance with histopathological grade. There is a better linear relation between mammographic- and pathological size of DCIS presented as microcalcifications than as a density, although both relations are statistically significant.

Radiography in acute ankle injuries: the Ottawa Ankle Rules versus local diagnostic decision rules.

STUDY OBJECTIVE: We validate the Ottawa Ankle Rules and 2 Dutch ankle rules in distinguishing clinically significant fractures from insignificant fractures and other injuries in patients with a painful ankle presenting to the emergency department. METHODS: This prospective comparison of 3 ankle rules was conducted in the ED of a 580-bed community teaching hospital in Amsterdam from January 1998 to April 1999. Participants included 647 consecutive patients aged 18 years or older presenting with a painful ankle after trauma. All physicians received extensive and pictorial training on how to correctly score the respective items of the rules. The physician on call recorded these items derived from history and physical examination on a standardized data sheet. All patients subsequently underwent standard radiographic assessment. A radiologist and a trauma surgeon evaluated the radiographs blinded from the results of the data sheet form and the treatment given. The diagnostic performance of the 3 rules was measured in terms of sensitivity, specificity, and the reduction of radiographs. Receiver operating characteristic (ROC) curves were constructed, and the area under the ROC curves was calculated and compared. RESULTS: Seventy-four fractures were seen, of which 41 were clinically significant. The Ottawa Ankle Rules had a sensitivity of 98% for identifying clinically significant fractures; the local rules scored 88% and 59%, respectively. The potential savings in radiographs for the 3 decision rules were 24%, 54%, and 82%, respectively. The area under the ROC curve was better for both the local rules (0.84 and 0.83) compared with the Ottawa Ankle Rules (0.76). CONCLUSION: Because the identification of all relevant fractures is more important than a reduction in radiographs, the higher sensitivity of the Ottawa Ankle Rules makes these most suitable for implementation in The Netherlands.

Comparison of diagnostic decision rules and structured data collection in assessment of acute ankle injury.

BACKGROUND: Ankle decision rules help to determine which patients with ankle injuries should undergo radiography. However, these rules are limited by imperfect generalizability and sensitivity. The judgement of physicians, aided by structured data collection, is a potential alternative. We compared the diagnostic performance of 2 decision rules with the performance of physicians, aided by structured data collection, in ruling out fracture in patients with acute ankle injury. METHODS: Consecutive patients with acute ankle injury who visited the emergency department of a teaching community hospital in Amsterdam were included in the study. After taking the patient's history and performing a physical examination, the surgical resident in each case completed a specially developed structured data form incorporating all of the variables in the Ottawa and Leiden ankle rules, as well as some additional variables. The form then asked whether the resident thought radiography was necessary. Each patient then underwent ankle and midfoot radiography. The films were independently interpreted by a radiologist and a trauma surgeon, who were both blinded to the information on the data form. Sensitivity, specificity and the percentage of patients for whom radiography was recommended were the main outcome measures. RESULTS: Of 690 consecutive patients, 647 met the inclusion criteria. Fractures were observed in 74 (11%) of these patients. Sensitivity was 89% (95% confidence interval [CI] 80% to 95%) for the Ottawa ankle rules, 80% (95% CI 69% to 88%) for the Leiden ankle rule and 82% (95% CI 72% to 90%) for physicians' judgement. Specificity was 26% (95% CI 23% to 30%), 59% (95% CI 55% to 63%) and 68% (95% CI 64% to 71%) respectively. Radiography was recommended in 76% (95% CI 72% to 79%), 46% (95% CI 42% to 50%) and 38% (95% CI 34% to 42%) of cases respectively. The Ottawa rules missed 8 fractures, of which 1 was clinically significant, the Leiden rule missed 15 fractures, of which 5 were clinically significant, and the residents missed 13 fractures, of which 1 was clinically significant. INTERPRETATION: Physicians' judgement, aided by structured data collection, was similar to existing international and local decision rules in terms of sensitivity in identifying cases requiring radiography and may outperform these prediction rules in terms of minimizing radiographic examinations for patients with ankle trauma.