Long-Term Functional Outcome After Early vs. Late Stoma Closure in Rectal Cancer Surgery: Sub-analysis of the Multicenter FORCE Trial.

PURPOSE: The aim of this study was to assess the effect of early stoma closure on bowel function after low anterior resection (LAR) for rectal cancer. METHODS: Patients participating in the FORCE trial who underwent LAR with protective stoma were included in this study. Patients were subdivided into an early closure group (< 3 months) and late closure group (> 3 months). Endpoints of this study were the Wexner Incontinence, low anterior resection syndrome (LARS), EORTC QLQ-CR29, and fecal incontinence quality of life (FIQL) scores at 1 year. RESULTS: Between 2017 and 2020, 38 patients had received a diverting stoma after LAR for rectal cancer and could be included. There was no significant difference in LARS (31 vs. 30, p = 0.63) and Wexner score (6.2 vs. 5.8, p = 0.77) between the early and late closure groups. Time to stoma closure in days was not a predictor for LARS (R2 = 0.001, F (1,36) = 0.049, p = 0.83) or Wexner score (R2 = 0.008, F (1,36) = 0.287, p = 0.60) after restored continuity. There was no significant difference between any of the FIQL domains of lifestyle, coping, depression, and embarrassment. In the EORTC QLQ-29, body image scored higher in the late closure group (21.3 vs. 1.6, p = 0.004). CONCLUSION: Timing of stoma closure does not appear to affect long-term bowel function and quality of life, except for body image. To improve functional outcome, attention should be focused on other contributing factors.

Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase 3 CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase 3 trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1:1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n= 103 without upfront PTR, n=101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (IQR 59-71). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% CI 16.0-22.2) compared to 20.1 months (95% CI 17.0-25.1) in the upfront PTR arm (p = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (p=0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSION: of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Implementation of Pelvic Floor Rehabilitation after rectal cancer surgery: A qualitative study guided by the Consolidated Framework for Implementation Research (CFIR).

BACKGROUND: Pelvic Floor Rehabilitation (PFR) is effective in a selection of patients with low anterior resection syndrome (LARS) after rectal cancer surgery. This study aimed to identify barriers and enablers to prepare for successful implementation into clinical practice. METHODS: A qualitative study was performed, guided by the Consolidated Framework for Implementation Research (CFIR). Individual interviews (n = 27) and two focus groups were conducted to synthesize the perspectives of rectal cancer patients, pelvic floor (PF) physiotherapists, and medical experts. RESULTS: Barriers were found to be the absence of guidelines about LARS treatment, underdeveloped network care, suboptimal patient information, and expectation management upfront to PFR. Financial status is frequently a barrier because insurance companies do not always reimburse PFR. Enablers were the current level of evidence for PFR, the positive relationship between patients and PF physiotherapists, and the level of self-motivation by patients. CONCLUSION: The factors identified in our study play a crucial role in ensuring a successful implementation of PFR after rectal cancer surgery.

Pelvic Floor Rehabilitation After Rectal Cancer Surgery One-year follow-up of a Multicenter Randomized Clinical Trial (FORCE trial).

OBJECTIVE: This study aims to evaluate the effects of pelvic floor rehabilitation (PFR) after low anterior resection (LAR) at one-year follow-up. SUMMARY BACKGROUND DATA: After LAR, with restoration of bowel continuity, up to 90% of patients develop anorectal dysfunction, significantly impacting their quality of life. However, standardized treatment is currently unavailable. The FORCE trial demonstrated the beneficial effects of PFR after three months regarding specific domains of the Fecal Incontinence QoL (FIQL) questionnaire and urgency compared to usual care. METHODS: The FORCE trial is a multicenter, two-arm, randomized clinical trial. All patients undergoing LAR were randomly assigned to receive either usual care or a standardized PFR program. The primary outcome measure is the Wexner incontinence score, and the secondary endpoints included the LARS score, the EORTC colorectal-specific QoL questionnaire, and health- and fecal incontinence-related QoL. Assessments were conducted at baseline before randomization, at three months and one-year follow-ups. RESULTS: A total of 86 patients were included (PFR: n=40, control: n=46). After one year, PFR did not significantly improve Wexner incontinence scores (PFR: -3.33, 95% CI -4.41 to -2.26, control: -2.54, 95% CI -3.54 to -1.54, P=0.30). Similar to the three-month follow-up, patients without near-complete incontinence at baseline showed sustained improvement in fecal incontinence (PFR: -2.82, 95% CI -3.86 to -1.76, control: -1.43, 95% CI -2.36 to -0.50, P=0.06). Significant improvement was reported in the FIQL domains Lifestyle (PFR: 0.51, control: -0.13, P=0.03) and Coping and Behavior (PFR: 0.40, control: -0.24, P=0.01). CONCLUSION: At one-year follow-up, no significant differences were found in fecal incontinence scores; however, PFR was associated with improved fecal incontinence related QoL compared to usual care.

Relief of Obstruction in Left-Sided Obstructive Colon Cancer: Nationwide Analysis of Applied Treatment in the Palliative Setting.

BACKGROUND: For relief of bowel obstruction in left-sided obstructive colon cancer (LSOCC), a self-expandable metal stent (SEMS) or decompressing stoma (DS) can be placed. In a curative setting, these two strategies have been extensively studied as a bridge to elective resection. Guidelines recommend SEMS as the preferred option in the palliative setting, but adherence in daily practice is unknown. Therefore, this study aimed to gain more insight into patients with LSOCC who received palliative treatment with SEMS or DS at a national level. METHODS: A retrospective population-based cohort study was conducted in the Netherlands. Data from the Netherlands Cancer Registry (NCR) on all patients with LSOCC treated with DS or SEMS not followed by resection of the primary tumour between January 1, 2015, and December 31, 2019, were analysed. Type of treatment (DS or SEMS) for different clinical scenarios, was the main outcome of this study, and was also evaluated over the years (2015-2019). RESULTS: Palliative treatment with SEMS or DS for LSOCC was performed in 1077 patients, of whom 79.2% had metastatic disease (M1). Patients without metastatic disease (M0) were older (≥ 80 years M0 67.4%, M1 25.3%, P < 0.001), had a worse clinical condition (ASA III 51.4% versus 36.37%, ASA IV-V 13.3% versus 4.0% P < 0.001) and presented with higher tumour stage (cT4 55.4% versus 33.5%, % P < 0.001). DS was performed in 91.5% of the patients and SEMS in 8.5%. The proportion of DS did not significantly differ between patients with M1 and M0 (91.8% vs. 90.2% respectively, P = 0.525). No increase in SEMS application was observed over the years, with a stable overall proportion of DS of 91-92% per year. In the multivariable analyses, ninety-day mortality and overall survival were not significantly different between SEMS and DS. CONCLUSIONS: This study revealed that DS was the primary treatment modality for palliative management of LSOCC in the Netherlands between 2015 and 2019, while the guidelines recommended SEMS as preferred treatment. For patients with LSOCC eligible for stenting in the palliative setting, SEMS placement should become more available and accessible as the preferred treatment option, to avoid a stoma in the terminal phase of life.

Five-Year Follow-Up of a Slowly Resorbable Biosynthetic P4HB Mesh (Phasix) in VHWG Grade 3 Incisional Hernia Repair.

Objective: To assess the 5-year recurrence rate of incisional hernia repair in Ventral Hernia Working Group (VHWG) 3 hernia with a slowly resorbable mesh. Summary Background Data: Incisional hernia recurs frequently after initial repair. In potentially contaminated hernia, recurrences rise to 40%. Recently, the biosynthetic Phasix mesh has been developed that is resorbed in 12-18 months. Resorbable meshes might be a solution for incisional hernia repair to decrease short- and long-term (mesh) complications. However, long-term outcomes after resorption are scarce. Methods: Patients with VHWG grade 3 incisional midline hernia, who participated in the Phasix trial (Clinilcaltrials.gov: NCT02720042) were included by means of physical examination and computed tomography (CT). Primary outcome was hernia recurrence; secondary outcomes comprised of long-term mesh complications, reoperations, and abdominal wall pain [visual analogue score (VAS): 0-10]. Results: In total, 61/84 (72.6%) patients were seen. Median follow-up time was 60.0 [interquartile range (IQR): 55-64] months. CT scan was made in 39 patients (68.4%). A recurrence rate of 15.9% (95% confidence interval: 6.9-24.8) was calculated after 5 years. Four new recurrences (6.6%) were found between 2 and 5 years. Two were asymptomatic. In total, 13/84 recurrences were found. No long-term mesh complications and/or interventions occurred. VAS scores were 0 (IQR: 0-2). Conclusions: Hernia repair with Phasix mesh in high-risk patients (VHWG 3, body mass index >28) demonstrated a recurrence rate of 15.9%, low pain scores, no mesh-related complications or reoperations for chronic pain between the 2- and 5-year follow-up. Four new recurrences occurred, 2 were asymptomatic. The poly-4-hydroxybutyrate mesh is a safe mesh for hernia repair in VHWG 3 patients, which avoids long-term mesh complications like pain and mesh infection.

Risk factors for a permanent stoma after resection of left-sided obstructive colon cancer - A prediction model.

INTRODUCTION: In patients with left-sided obstructive colon cancer (LSOCC), a stoma is often constructed as part of primary treatment, but with a considerable risk of becoming a permanent stoma (PS). The aim of this retrospective multicentre cohort is to identify risk factors for a PS in LSOCC and to develop a pre- and postoperative prediction model for PS. MATERIALS AND METHODS: Data was retrospectively obtained from 75 hospitals in the Netherlands. Patients who had curative resection of LSOCC between January 1, 2009 to December 31, 2016 were included with a minimum follow-up of 6 months after resection. The interventions analysed were emergency resection, decompressing stoma or stent as bridge-to-elective resection. Main outcome measure was presence of PS at the end of follow-up. Multivariable logistic regression analysis was performed to identify risk factors for PS at primary presentation (T0) and after resection, in patients having a stoma in situ (T1). These risk factors were used to construct a web-based prediction tool. RESULTS: Of 2099 patients included in the study (T0), 779 had a PS (37%). A total of 1275 patients had a stoma in situ directly after resection (T1), of whom 674 had a PS (53%). Median follow-up was 34 months. Multivariable analysis showed that older patients, female sex, high ASA-score and open approach were independent predictors for PS in both the T0 and T1 population. Other predictors at T0 were sigmoid location, low Hb, high CRP, cM1 stage, and emergency resection. At T1, subtotal colectomy, no primary anastomosis, not receiving adjuvant chemotherapy and high pTNM stage were additional predictors. Two predictive models were built, with an AUC of 0.74 for T0 and an AUC of 0.81 for T1. CONCLUSIONS: PS is seen in 37% of the patients who have resection of LSOCC. In patients with a stoma in situ directly after resection, 53% PS are seen due to non-reversal. Not only baseline characteristics, but also treatment strategies determine the risk of a PS in patients with LSOCC. The developed predictive models will give physicians insight in the role of the individual variables on the risk of a PS and help in informing the patient about the probability of a PS.

Outcomes of patients with perforated colon cancer: A systematic review.

INTRODUCTION: Perforated colon cancer (PCC) is a distinct clinical entity with implications for treatment and prognosis, however data on PCC seems scarce. The aim of this systematic review is to provide a comprehensive overview of the recent literature on clinical outcomes of PCC. MATERIALS AND METHODS: A systematic literature search of MEDLINE (PubMed), Embase, Cochrane library and Google scholar was performed. Studies describing intentionally curative treatment for patients with PCC since 2010 were included. The main outcome measures consisted of short-term surgical complications and long-term oncological outcomes. RESULTS: Eleven retrospective cohort studies were included, comprising a total of 2696 PCC patients. In these studies, various entities of PCC were defined. Comparative studies showed that PCC patients as compared to non-PCC patients have an increased risk of 30-day mortality (8-33% vs 3-5%), increased post-operative complications (33-56% vs 22-28%), worse overall survival (36-40% vs 48-65%) and worse disease-free survival (34-43% vs 50-73%). Two studies distinguished free-perforations from contained perforations, revealing that free-perforation is associated with significantly higher 30-day mortality (19-26% vs 0-10%), lower overall survival (24-28% vs 42-64%) and lower disease-free survival (15% vs 53%) as compared to contained perforations. CONCLUSION: Data on PCC is scarce, with various PCC entities defined in the studies included. Heterogeneity of the study population, definition of PCC and outcome measures made pooling of the data impossible. In general, perforation, particularly free perforation, seems to be associated with a substantial negative effect on outcomes in colon cancer patients undergoing surgery. Better definition and description of the types of perforation in future studies is essential, as outcomes seem to differ between types of PCC and might require different treatment strategies.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

Pelvic Floor Rehabilitation After Rectal Cancer Surgery: A Multicenter Randomized Clinical Trial (FORCE Trial).

OBJECTIVE: To investigate the effects of PFR after LAR compared to usual care without PFR. SUMMARY OF BACKGROUND DATA: Functional complaints, including fecal incontinence, often occur after LAR for rectal cancer. Controversy exists about the effectiveness of PFR in improving such postoperative functional outcomes. METHODS: This was a multicenter, randomized controlled trial involving 17 Dutch centers. Patients after LAR for rectal cancer were randomly assigned (1:1) to usual care or PFR and stratified by sex and administration of neoadjuvant therapy. Selection was not based on severity of complaints at baseline. Baseline measurements were taken 3 months after surgery without temporary stoma construction or 6 weeks after stoma closure. The primary outcome measure was the change in Wexner incontinence scores 3 months after randomization. Secondary outcomes were fecal incontinence-related quality of life, colorectal-specific quality of life, and the LARS scores. RESULTS: Between October 2017 and March 2020, 128 patients were enrolled and 106 randomly assigned (PFR n = 51, control n = 55); 95 patients (PFR n = 44, control n = 51) were assessable for final analysis. PFR did not lead to larger changes in Wexner incontinence scores in nonselected patients after LAR compared to usual care [PFR: -2.3, 95% confidence interval (CI) -3.3 to -1.4, control: -1.3, 95% CI -2.2 to -0.4, P = 0.13]. However, PFR was associated with less urgency at follow-up (odds ratio 0.22, 95% CI 0.06-0.86). Patients without near-complete incontinence reported larger Wexner score improvements after PFR (PFR: -2.1, 95% CI -3.1 to -1.1, control: -0.7, 95% CI -1.6 to 0.2, P = 0.045). For patients with at least moderate incontinence PFR resulted in relevant improvements in all fecal incontinence-related quality of life domains, while the control group deteriorated. These improvements were even larger when patients with near-complete incontinence were excluded. No serious adverse PFR-related events occurred. CONCLUSION: No benefit was found of PFR in all patients but several subgroups were identified that did benefit from PFR, such as patients with urgency or with at least moderate incontinence and no near-complete incontinence. A selective referral policy (65%-85% of all patients) is suggested to improve postoperative functional outcomes for patients after LAR for rectal cancer. TRIAL REGISTRATION: Netherlands Trial Registration, NTR5469, registered on 3 September 2015.

Changes in rectal cancer treatment after the introduction of a national screening program; Increasing use of less invasive strategies within a national cohort.

AIM: Organ preserving treatment strategies and the introduction of a colorectal cancer-screening program have likely influenced the resection rates of rectal cancer. The aim of this study is to assess the influence of these developments on rectal cancer treatment and resection rates in the Netherlands. METHODS: Patients diagnosed with non-metastatic rectal cancer between 2013 and 2018, were selected from the Netherlands Cancer Registry. The distribution of surgical and neo-adjuvant treatment and resection rates were analyzed and compared over time. RESULTS: Between 2013 and 2018 22640 patients were diagnosed with non-metastatic rectal cancer. The incidence of early stage (cT1) disease increased from 141 (4%) in 2013 to 448 (12%) in 2018. The use of neoadjuvant radiotherapy and chemo-radiotherapy dropped from 39% to 21% and 34%-25%, respectively. A decrease in surgical resection rates (including TEM) was observed from 85% to 73%. The proportion of patients who underwent endoscopic resections increased from 3% to 10%. The decrease in surgical resection rates was larger in patients treated with neo-adjuvant chemo-radiotherapy. CONCLUSION: An increase in stage I disease is noted after the introduction of the screening program. Surgical resection rates for rectal cancer have fallen over time. Endoscopic resections due to more early-stage disease probably accounts for a large part of this decline. Furthermore, a watch and wait approach after neo-adjuvant chemo-radiotherapy may play an important role as well.

Impact of the COVID-19 pandemic on surgical care in the Netherlands.

BACKGROUND: The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. METHODS: A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. RESULTS: Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). CONCLUSION: The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.

COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018­2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

Slowly resorbable biosynthetic mesh: 2-year results in VHWG grade 3 hernia repair.

INTRODUCTION: Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months. METHODS: A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm2, scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months. RESULTS: Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery. CONCLUSION: After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations. TRIAL REGISTRATION: Registered on clinicaltrials.gov (NCT02720042), March 25, 2016.

Survival following surgical treatment for anorectal melanoma seems similar for local excision and extensive resection regardless of nodal involvement.

BACKGROUND: Anorectal melanoma is a rare malignancy with a dismal prognosis. The purpose of this study was to investigate whether the survival per stage is influenced by the surgical approaches (local excision or extensive resection), to assess prognostic factors of survival, and to answer the question whether the practiced surgical approaches changed over time. METHODS: Dutch cancer registry organizations (IKNL and PALGA) were queried for all patients with a diagnosis of anorectal melanoma (1989-2019). Patients with disseminated disease at diagnosis were excluded. Survival outcomes were compared for the two surgical approaches stratified by stage (clinical node negative (cN0) and clinical node positive (cN+)) and date of diagnosis. RESULTS: A total of 103 patients were included in this study. In both cN0 and cN+ patients the surgical strategy did not significantly influence survival (cN0: 21.7% 5-year survival, median 25 months for local excision versus 13.7% 5-year survival, median 17 months for extensive resection (p = 0.228), cN+: 11.1% 5-year survival for local excision, median 17 months versus 8.7% 5-year survival, median 14 months for extensive resection (p = 0.741)). Stage and date of diagnosis showed to be prognostic factors of survival. The ratio between the two surgical approaches was unchanged over three decades. CONCLUSIONS: Extensive resection does not seem to improve survival in both cN0 and cN+ anorectal melanoma patients compared to local excision. However in the past three decades no shift towards local excision has been found. cN+ stage and an older date of diagnosis are predictors for worse survival.

Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15-20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. METHODS: This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009-2015) and cohort B (period 2015-2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. RESULTS: Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). CONCLUSION: Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.

Feasibility of volatile organic compound in breath analysis in the follow-up of colorectal cancer: A pilot study.

BACKGROUND: Colorectal carcinoma (CRC) has a worldwide incidence of 1.4 million patients and a large share in cancer-related mortality. After curative treatment, the risk of recurrence is 30-65%. Early detection may result in curative treatment. However, current follow-up (FU) examinations have low sensitivity ranging from 49 to 85% and are associated with high costs. Therefore, the search for a new diagnostic tool is justified. Analysis of volatile organic compound in exhaled air through an electronic nose (eNose) is a promising new patient-friendly diagnostic tool. We studied whether the eNose under investigation, the Aeonose™, is able to detect local recurrence or metastases of CRC. METHODS: In this cross-sectional study we included 62 patients, all of whom underwent curative treatment for CRC in the past 5 years. Thirty-six of them had no metastases and 26 had extraluminal local recurrence or metastases of CRC, detected during FU. Breath testing was performed and machine learning was used to predict extraluminal recurrences or metastases, and based on the receiver operating characteristics (ROC)-curve both sensitivity and specificity were calculated. RESULTS: The eNose identified extra luminal local recurrences or metastases of CRC with a sensitivity and specificity of 0.88 (CI 0.69-0.97) and 0.75 (CI 0.57-0.87), respectively, with an overall accuracy of 0.81. DISCUSSION: This eNose may be a promising tool in detecting extraluminal local recurrences or metastases in the FU of curatively treated CRC. However, a well-designed prospective study is warranted to show its accuracy and predictive value before it can be used in clinical practice.

MRI cT1-2 rectal cancer staging accuracy: a population-based study.

BACKGROUND: Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS). METHODS: Patients with cT1-2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value. RESULTS: Of 7382 registered patients with cT1-2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1-2 N1 respectively. CONCLUSION: This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1-2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.

ANTECEDENTES: Una adecuada estadificación mediante resonancia magnética nuclear (RMN) de los cánceres de recto en estadios precoces es esencial para la toma de decisiones en una era en la existen diferentes opciones de tratamiento preservadoras del recto. El objetivo de este estudio de base poblacional fue determinar la precisión de la estadificación mediante RMN del cáncer de recto precoz en la práctica diaria, ya sea combinada o no con la ecografía endorectal (endorectal ultrasound, ERUS). MÉTODOS: Los pacientes con cáncer de recto en estadio cT1-2 que se sometieron a resección local o resección total del mesorrecto (total mesorectal excision, TME) sin (quimio) radioterapia neoadyuvante fueron seleccionados a partir del registro auditado ColoRectal holandés, entre el 1 de enero de 2011 y el 31 de diciembre de 2018. La precisión de las imágenes se expresó como sensibilidad, especificidad y valores predictivos positivo y negativo (positive- and negative predicting value, PPV / NPV). RESULTADOS: De un total de 7.382 pacientes registrados con cáncer de recto en estadio cT1-2, se incluyeron 5.539 pacientes (5.288 solamente RMN, 251 RMN + ERUS; 1.059 cT1 y 4.480 cT2). Los pacientes pT1 fueron sobreestadificados cuando se utilizó únicamente la RMN en un 54,7% de los casos (792/1.448) y cuando se combinó RMN y ERUS en un 31,0% (36/116). La infraestadificación de pT2 ocurrió en un 8,2% (197/2.388) y en un 27,9% (31/111), respectivamente. La RMN utilizada como única prueba sobreestadificó los casos pN0 en el 17,3% (570/3.303) y el VPP del estadio cN0 fue del 76,3% (2.733/3.583). De los 834 pacientes con estadio pT1N0, potencialmente adecuado para la resección local, 253 pacientes (30,3%) se clasificaron correctamente como cT1N0, y 484 (58,8%) y 97 (11,6%) pacientes se sobreestadificaron como cT2N0 y cT1-2N1, respectivamente. CONCLUSIÓN: Este estudio de base poblacional holandés en pacientes que se sometieron a una resección local o a cirugía TME por cáncer de recto cT1-2 con estadificación preoperatoria mediante RMN, muestra una considerable sobreestadificación, lo que indica las debilidades y oportunidades en las estrategias de preservación del recto.