Impact of the new rectal cancer definition on multimodality treatment and interhospital variability: Results from a nationwide cross-sectional study.

AIM: This study aimed to determine the consequences of the new definition of rectal cancer for decision-making in multidisciplinary team meetings (MDT). The new definition of rectal cancer, the lower border of the tumour is located below the sigmoid take-off (STO), was implemented in the Dutch guideline in 2019 after an international Delphi consensus meeting to reduce interhospital variations. METHOD: All patients with rectal cancer according to the local MDT, who underwent resection in 2016 in the Netherlands were eligible for this nationwide collaborative cross-sectional study. MRI-images were rereviewed, and the tumours were classified as above or on/below the STO. RESULTS: This study registered 3107 of the eligible 3178 patients (98%), of which 2784 patients had an evaluable MRI. In 314 patients, the tumour was located above the STO (11%), with interhospital variation between 0% and 36%. Based on TN-stage, 175 reclassified patients with colon cancer (6%) would have received different treatment (e.g., omitting neoadjuvant radiotherapy, candidate for adjuvant chemotherapy). Tumour location above the STO was independently associated with lower risk of 4-year locoregional recurrence (HR 0.529; p = 0.030) and higher 4-year overall survival (HR 0.732; p = 0.037) compared to location under the STO. CONCLUSION: By using the STO, 11% of the prior MDT-based diagnosis of rectal cancer were redefined as sigmoid cancer, with potential implications for multimodality treatment and prognostic value. Given the substantial interhospital variation in proportion of redefined cancers, the use of the STO will contribute to standardisation and comparability of outcomes in both daily practice and trial settings.

Prognostic significance of MRI-detected extramural venous invasion according to grade and response to neo-adjuvant treatment in locally advanced rectal cancer A national cohort study after radiologic training and reassessment.

BACKGROUND: Detection of grade 3-4 extra mural venous invasion (mrEMVI) on magnetic resonance imaging (MRI) is associated with an increased distant metastases (DM)-rate. This study aimed to determine the impact of different grades of mrEMVI and their disappearance after neoadjuvant therapy. METHODS: A Dutch national retrospective cross-sectional study was conducted, including patients who underwent resection for rectal cancer in 2016 from 60/69 hospitals performing rectal surgery. Patients with a cT3-4 tumour ≤8 cm from the anorectal junction were selected and their MRI-scans were reassessed by trained abdominal radiologists. Positive mrEMVI grades (3 and 4) were analyzed in regard to 4-year local recurrence (LR), DM, disease-free survival (DFS) and overall survival (OS). RESULTS: The 1213 included patients had a median follow-up of 48 months (IQR 30-54). Positive mrEMVI was present in 324 patients (27%); 161 had grade 3 and 163 had grade 4. A higher mrEMVI stage (grade 4 vs grade 3 vs no mrEMVI) increased LR-risk (21% vs 18% vs 7%, <0.001) and DM-risk (49% vs 30% vs 21%, p < 0.001) and decreased DFS (42% vs 55% vs 69%, p < 0.001) and OS (62% vs 76% vs 81%, p < 0.001), which remained independently associated in multivariable analysis. When mrEMVI had disappeared on restaging MRI, DM-rate was comparable to initial absence of mrEMVI (both 26%), whereas LR-rate remained high (22% vs 9%, p = 0.006). CONCLUSION: The negative oncological impact of mrEMVI on recurrence and survival rates was dependent on grading. Disappearance of mrEMVI on restaging MRI decreased the risk of DM, but not of LR.

Value of Size and Malignant Features of Lateral Lymph Nodes in Risk Stratification at Lateral Local Recurrence of Rectal Cancer: A National Cohort Study.

BACKGROUND: Patients with rectal cancer who have enlarged lateral lymph nodes (LLNs) have an increased risk of lateral local recurrence (LLR). However, little is known about prognostic implications of malignant features (internal heterogeneity, irregular margins, loss of fatty hilum, and round shape) on MRI and number of enlarged LLNs, in addition to LLN size. METHODS: Of the 3,057 patients with rectal cancer included in this national, retrospective, cross-sectional cohort study, 284 with a cT3-4 tumor located ≤8 cm from the anorectal junction who received neoadjuvant treatment and who had visible LLNs on MRI were selected. Imaging was reassessed by trained radiologists. LLNs were categorized based on size. Influence of malignant features and the number of LLNs on LLR was investigated. RESULTS: Of 284 patients with at least 1 visible LLN, 122 (43%) had an enlarged node (≥7.0 mm) and 157 (55%) had malignant features. Of the 122 patients with enlarged nodes, 25 had multiple (≥2). In patients with a single enlarged node (n=97), a single malignant feature was associated with a 4-year LLR rate of 0% and multiple malignant features was associated with a rate of 17% (P=.060). In the group with multiple malignant features, their disappearance on restaging was associated with an LLR rate of 13% compared with an LLR rate of 20% for persistent malignant features (P=.532). The presence of intermediate-size LLNs (5.0-6.9 mm) with at least 1 malignant feature was associated with a 4-year LLR rate of 8%; the 4-year LLR rate was 13% when the malignant features persisted on restaging MRI (P=.409). Patients with multiple enlarged LLNs had a 4-year LLR rate of 28% compared with 11% for those with a single enlarged LLN (P=.059). CONCLUSIONS: The presence of multiple enlarged LLNs (≥7.0 mm), as well as multiple malignant features in an enlarged node contribute to the risk of developing an LLR. These radiologic features can be used for clinical decision-making regarding the potential benefit of LLN dissection.

MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer: A Population-Based Cross-sectional Study With Standardized Radiological Evaluation After Dedicated Training.

BACKGROUND: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter, and location of lateral lymph nodes. OBJECTIVE: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI, and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training. DESIGN: Retrospective population-based cross-sectional study. SETTINGS: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals. PATIENTS: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had a cT3-4 tumor located ≤8 cm from the anorectal junction, of whom 891 received neoadjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence and (ipsi) lateral local recurrence rates. RESULTS: Re-review identified 314 patients (35%) with visible lateral lymph nodes. Of these, 30 patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes, and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (≥7 mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%; p <.001) and lateral local recurrence (14.7%, 4.4%, 0%; p < 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (HR 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (HR 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year lateral local recurrence rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were found to be associated with higher univariate 4-year distant metastasis rates (36.4% vs 24.4%; p = 0.021), but this was not significant in multivariable analyses (HR 1.3 [0.9-1.]) and did not worsen overall survival. LIMITATIONS: This study was limited by the retrospective design and total number of patients with lateral lymph nodes. CONCLUSIONS: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without the prognostic impact of downsizing after neoadjuvant therapy. These results point toward the incorporation of primary lateral lymph node size into treatment planning. See Video Abstract. IMPLICACIONES PRONSTICAS DE LOS NDULOS LINFTICOS LATERALES EN EL CNCER DE RECTO UN ESTUDIO TRANSVERSAL DE BASE POBLACIONAL CON EVALUACIN RADIOLGICA ESTANDARIZADA DESPUS DE UN ENTRENAMIENTO ESPECFICO: ANTECEDENTES:Hay una discusión en curso acerca de las implicaciones pronósticas de la presencia, el diámetro del eje corto y la ubicación de los nódulos linfáticos laterales.OBJETIVO:Analizar las características de los nódulos linfáticos laterales, el rol de la reducción de tamaño en la IRM de reestratificación y las tasas de recurrencia local asociadas para pacientes con cáncer de recto cT3-4 después de una nueva revisión y entrenamiento de IRM.DISEÑO:Estudio transversal retrospectivo poblacional.CONFIGURACIÓN:Este proyecto colaborativo fue dirigido por investigadores locales de los departamentos de cirugía y radiología en 60 hospitales holandeses.PACIENTES:3057 pacientes fueron operados de cáncer de recto en 2016: 1109 tenían tumor cT3-4 ubicado a ≤8 cm de la unión anorrectal de los cuales 890 recibieron terapia neoadyuvante.INTERVENCIONES(S):Ninguna.PRINCIPALES MEDIDAS DE RESULTADO:recurrencia local y tasas de recurrencia local ipsilateral.RESULTADOS:Una nueva revisión identificó a 314 pacientes (35%) con nódulos linfáticos laterales visibles. 30 de estos pacientes tenían solo nódulos obturadores estirados (n = 13) o ilíacos externos (n = 17) y ambos no provocaron recurrencias locales laterales. La presencia de nódulos linfáticos laterales ilíacos internos/obturadores (n = 284) dio como resultado tasas de recurrencia local y recurrencia local lateral a los 4 años del 16.4% y el 8.8%, respectivamente. Los nódulos linfáticos laterales agrandados (≥7 mm) (n = 122) resultaron en una mayor recurrencia local a los 4 años (20.8%, 13.1%, 0%, p < 0.001) y recurrencia local lateral (14.7%, 4.4%, 0%, p < 0.001) en comparación con nódulos linfáticos más pequeños y sin nódulos linfáticos laterales, respectivamente. Los nódulos linfáticos laterales visibles (índice de riesgo 1,8 (1,1-2,8)) y los nódulos linfáticos laterales agrandados (índice de riesgo 1.9 (1.1-3.5)) se asociaron de forma independiente con la recurrencia local en el análisis multivariable. Los nódulos linfáticos laterales agrandados con características malignas tuvieron tasas de recurrencia local lateral a 4 años más altas del 17.0%. La reducción de tamaño no tuvo impacto en las tasas de recurrencia local lateral. Los nódulos linfáticos laterales agrandados se asociaron con tasas univariadas más altas de metástasis a distancia a los 4 años (36.4%, 24.4%, p = 0.021), pero no en el análisis multivariable (índice de riesgo 1.3 (0.9-1.8)), y no empeoró la supervivencia general.LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo y el número total de pacientes con nódulos linfáticos laterales.CONCLUSIONES:Se confirmó el riesgo de recurrencia local lateral debido a los nódulos linfáticos laterales (agrandados), pero sin el impacto pronóstico de la reducción después de la terapia neoadyuvante. Estos resultados apuntan hacia la incorporación del tamaño del nódulo linfático lateral primario en la planificación del tratamiento. (Traducción-Dr. Aurian Garcia Gonzalez ).

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes.

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates. Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

A Deep Learning Framework with Explainability for the Prediction of Lateral Locoregional Recurrences in Rectal Cancer Patients with Suspicious Lateral Lymph Nodes.

Malignant lateral lymph nodes (LLNs) in low, locally advanced rectal cancer can cause (ipsi-lateral) local recurrences ((L)LR). Accurate identification is, therefore, essential. This study explored LLN features to create an artificial intelligence prediction model, estimating the risk of (L)LR. This retrospective multicentre cohort study examined 196 patients diagnosed with rectal cancer between 2008 and 2020 from three tertiary centres in the Netherlands. Primary and restaging T2W magnetic resonance imaging and clinical features were used. Visible LLNs were segmented and used for a multi-channel convolutional neural network. A deep learning model was developed and trained for the prediction of (L)LR according to malignant LLNs. Combined imaging and clinical features resulted in AUCs of 0.78 and 0.80 for LR and LLR, respectively. The sensitivity and specificity were 85.7% and 67.6%, respectively. Class activation map explainability methods were applied and consistently identified the same high-risk regions with structural similarity indices ranging from 0.772-0.930. This model resulted in good predictive value for (L)LR rates and can form the basis of future auto-segmentation programs to assist in the identification of high-risk patients and the development of risk stratification models.

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting.

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection. RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874). CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Coverage of Lateral Lymph Nodes in Rectal Cancer Patients with Routine Radiation Therapy Practice and Associated Locoregional Recurrence Rates.

PURPOSE: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for the occurrence of ipsilateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiation therapy practice in the Netherlands and associated LLR rates. METHODS AND MATERIALS: Patients with a primary tumor ≤8 cm of the anorectal junction, cT3-4 stage, and at least 1 internal iliac or obturator LLN with short axis ≥5 mm who received neoadjuvant (chemo)radiation therapy, were selected from a national, cross-sectional study of patients with rectal cancer treated in the Netherlands in 2016. Magnetic resonance images and radiation therapy treatment plans were reviewed regarding segmented LLNs as gross tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiation therapy dose. RESULTS: A total of 223 out of 3057 patients with at least 1 LLN ≥5 mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received ≥95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared with those inside (4.0% vs 12.5%, P = .092) or when receiving <95% versus ≥95% of the planned radiation therapy dose (7.1% vs 11.3%, P = .843), respectively. Two of 7 patients who received a dose escalation of 60 Gy developed an LLR (4-year LLR rate of 28.6%). CONCLUSIONS: This evaluation of routine radiation therapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further.

Significant improvement after training in the assessment of lateral compartments and short-axis measurements of lateral lymph nodes in rectal cancer.

OBJECTIVES: In patients with rectal cancer, the size and location of lateral lymph nodes (LLNs) are correlated to increased lateral local recurrence rates. Sufficient knowledge and accuracy when measuring these features are therefore essential. The objective of this study was to evaluate the variation in measurements and anatomical classifications of LLNs before and after training. METHODS: Fifty-three Dutch radiologists examined three rectal MRI scans and completed a questionnaire. Presence, location, size, and suspiciousness of LLNs were reported. This assessment was repeated after a 2-hour online training by the same radiologists with the same three cases plus three additional cases. Three expert radiologists independently evaluated these 6 cases and served as the standard of reference. RESULTS: Correct identification of the anatomical location improved in case 1 (62 to 77% (p = .077)) and in case 2 (46 to 72% (p = .007)) but decreased in case 3 (92 to 74%, p = .453). Compared to the first three cases, cases 4, 5, and 6 all had a higher initial consensus of 73%, 79%, and 85%, respectively. The mean absolute deviation of the short-axis measurements in cases 1-3 were closer-though not significantly-to the expert reference value after training with reduced ranges and standard deviations. Subjective determination of malignancy had a high consensus rate between participants and experts. CONCLUSION: Though finding a high consensus rate for determining malignancy of LLNs, variation in short-axis measurements and anatomical location classifications were present and improved after training. Adequate training would support the challenges involved in evaluating LLNs appropriately. KEY POINTS: • Variation was present in the assessment of the anatomical location and short-axis size of lateral lymph nodes. • In certain cases, the accuracy of short-axis measurements and anatomical location, when compared to an expert reference value, improved after a training session. • Consensus before and after training on whether an LLN was subjectively considered to be suspicious for malignancy was high.

Retrospective evaluation of national MRI reporting quality for lateral lymph nodes in rectal cancer patients and concordance with prospective re-evaluation following additional training.

OBJECTIVES: The presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in MRI reports is therefore essential. This study assessed whether LLNs were mentioned in primary MRI reports at a national level and investigated the concordance with standardised re-review. METHODS: This national, retrospective, cross-sectional cohort study included 1096 patients from 60 hospitals treated in 2016 for primary cT3-4 rectal cancer ≤ 8 cm from the anorectal junction. Abdominal radiologists re-reviewed all MR images following a 2-h training regarding LLNs. RESULTS: Re-review of MR images identified that 41.0% of enlarged (≥ 7 mm) LLNs were not mentioned in primary MRI reports. A contradictory anatomical location was stated for 73.2% of all LLNs and a different size (≥/< 7 mm) for 41.7%. In total, 49.4% of  all cases did not mention LLNs in primary MRI reports. Reporting LLNs was associated with stage (cT3N0 44.3%, T3N+/T4 52.8%, p = 0.013), cN stage (N0 44.1%, N1 48.6%, N2 59.5%, p < 0.001), hospital type (non-teaching 34.6%, teaching 52.2%, academic 53.2% p = 0.006) and annual rectal cancer resection volumes (low 34.8%, medium 47.7%, high 57.3% p < 0.001). For LLNs present according to original MRI reports (n = 226), 64.2% also mentioned a short-axis size, 52.7% an anatomical location and 25.2% whether it was deemed suspicious. CONCLUSIONS: Almost half of the primary MRI reports for rectal cancer patients treated in the Netherlands in 2016 did not mention LLNs. A significant portion of enlarged LLNs identified during re-review were also not mentioned originally, with considerable discrepancies for location and size. These results imply insufficient awareness and indicate the need for templates, education and training.

Lateral Lymph Nodes in Rectal Cancer: Do we all Think the Same? A Review of Multidisciplinary Obstacles and Treatment Recommendations.

Lateral lymph nodes in low, locally advanced, rectal cancer have proven implications for local recurrence rates, which increase drastically in the presence of persistently enlarged lateral lymph nodes. These clinical implications warrant a thorough understanding of lateral nodal disease with awareness and knowledge from all three specialties involved - radiology, radiation oncology, and surgery - to ensure proper treatment. Relevant literature for each specialty, including all current guidelines and perspectives, were examined. Variations in definitions and treatment paradigms were evaluated. There is still no consensus for the standardized treatment of lateral nodal disease. Each discipline works according to their own available evidence, but relevant data are scarce. Current international guidelines and standard recommendations for the diagnostics and treatment of lateral lymph nodes are lacking. This results in differing perspectives and interpretations between the disciplines which can lead to challenging communication in an area where multidisciplinary collaboration is essential. This review addresses this by presenting the current evidence, perspectives and practices of each specialty and makes suggestions for each phase of the diagnostic and treatment process for patients with lateral nodal disease. By doing this, steps are taken toward achieving international consensus, and multidisciplinary collaboration.

Fibrosis and MAGNIFI-CD Activity Index at Magnetic Resonance Imaging to Predict Treatment Outcome in Perianal Fistulizing Crohn's Disease Patients.

BACKGROUND AND AIMS: Characteristic magnetic resonance imaging [MRI] features associated with long-term perianal fistula closure are still being discussed. This study evaluated the predictive value of degree of fibrosis and disease activity (MAGNIFI-CD index) at MRI for long-term clinical closure of Crohn's perianal fistulas. METHODS: Crohn's disease [CD] patients treated with surgical closure following anti-tumour necrosis factor [anti-TNF] induction or anti-TNF alone for high perianal fistulas as part of a patient preference randomized controlled trial [PISA-II] between 2013 and 2020 with a post-treatment MRI and long-term clinical follow-up data were retrospectively included. Two radiologists scored the degree of fibrosis and MAGNIFI-CD index at pre- and post-treatment MRI. The accuracy of post-treatment MRI findings in predicting long-term clinical closure [12 months after the MRI] was evaluated using receiver operating characteristics [ROC] analysis. RESULTS: Fifty patients were included: 31 female, median age 33 years (interquartile range [IQR] 26-45). Fourteen patients showed a 100% fibrotic fistula at post-treatment MRI, all of which had long-term clinical closure. Median MAGNIFI-CD index at post-treatment MRI was 0 [IQR 0-5] in 25 patients with long-term clinical closure and 16 [IQR 10-20] in 25 patients without. ROC analysis showed an area under the curve of 0.90 (95% confidence interval [CI] 0.82-0.99) for degree of fibrosis and 0.95 [95% CI 0.89-1.00] for the MAGNIFI-CD index, with a Youden cut-off point of 6 [91% specificity, 87% sensitivity]. CONCLUSIONS: Degree of fibrosis and MAGNIFI-CD index at post-treatment MRI are accurate in predicting long-term clinical closure and seem valuable in follow-up of perianal CD. A completely fibrotic tract at MRI is a robust indicator for long-term fistula closure. EUDRACT: 2013-002932-25 and 2018-002064-15.

Evaluation of the implementation of the sigmoid take-off landmark in the Netherlands.

AIM: The sigmoid take-off (STO), the point on imaging where the sigmoid sweeps ventral from the sacrum, was chosen as the definition of the rectum during an international Delphi consensus meeting and has been incorporated into the Dutch guidelines since October 2019. The aim of this study was to evaluate the implementation of this landmark 1 year after the guideline implementation and to perform a quality assessment of the STO training. METHOD: Dutch radiologists, surgeons, surgical residents, interns, PhD students and physician assistants were asked to complete a survey and classify 20 tumours on MRI as 'below', 'on' or 'above' the STO. Outcomes were agreement with the expert reference, inter-rater variability and accuracy before and after the training. RESULTS: Eighty-six collaborators participated. Six radiologists (32%) and 11 surgeons (73%) used the STO as the standard landmark to distinguish between rectal and sigmoidal tumours during multidisciplinary meetings. Overall agreement with the expert reference improved from 53% to 70% (p < 0.001) after the training. The positive predictive value for diagnosing rectal tumours was high before and after the training (92% vs. 90%); the negative predictive value for diagnosing sigmoidal tumours improved from 39% to 63%. CONCLUSION: Approximately half of the represented hospitals have implemented the new definition of rectal cancer 1 year after the implementation of the Dutch national guidelines. Overall baseline agreement with the expert reference and accuracy for the tumours around the STO was low, but improved significantly after training. These results highlight the added value of training in implementation of radiological landmarks to ensure unambiguous assessment.

Multidisciplinary management of early rectal cancer - The role of surgical local excision in current and future clinical practice.

The implementation of bowel cancer screening programs has led to a rise in the incidence of early rectal cancer. The combination of increased incidence and the growing interest in organ-sparing treatment options has led to an amplified importance of local excision techniques in treatment strategies for early rectal cancer. In addition, developments in new technologies of single-port surgery have popularized surgical techniques. Although local treatment of early rectal cancer seems promising, a multidisciplinary approach is necessary and awareness of the oncological robustness is warranted to enable shared decision-making. This review illustrates the position of surgical local excision in the treatment of early rectal cancer and reflects on its role in current and future clinical practice.

Fasted and fed small bowel motility patterns at cine-MRI in chronic intestinal pseudo-obstruction.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe intestinal motility disorder of which the pathophysiology is largely unknown. This study aimed at gaining insight in fasted and fed small bowel motility in CIPO patients using cine-MRI with caloric stimulation. METHODS: Eight adult patients with manometrically confirmed CIPO were prospectively included. Patients underwent a cine-MRI protocol after an overnight fast, comprising fasting-state scans and scans after ingestion of a meal (Nutridrink, 300 kcal). Small bowel motility was quantified resulting in a motility score in arbitrary units (AU) and visually assessed by three radiologists. Findings were compared with those in 16 healthy volunteers. KEY RESULTS: Motility scores (median, IQR) in CIPO patients were 0.21 (0.15-0.30) in the fasting state and 0.23 (0.15-0.27) directly postprandially. In healthy volunteers, corresponding motility scores were 0.15 (0.13-0.18) and 0.22 (0.19-0.25), respectively. The postprandial change in motility score was +1% (-19 to +21%) in CIPO and +39% (+23 to +50%) in healthy volunteers (p = 0.001*). Visual analysis revealed increased small bowel contractility in four, normal in two, and decreased in two CIPO patients. CONCLUSIONS & INFERENCES: Surprisingly, we found hyperactive small bowel motility in half of the CIPO patients, suggestive of uncoordinated motility. A wide variation in motility patterns was observed, both higher, lower, and comparable contractility compared with healthy subjects. No clear postprandial activation was seen in patients. Cine-MRI helps to gain insight in this complex disease and can potentially impact treatment decisions in the future.

Comparison of contrast-enhanced and diffusion-weighted MRI in assessment of the terminal ileum in Crohn's disease patients.

PURPOSE: The purpose of the study was to compare the performance of contrast-enhanced (CE)-MRI and diffusion-weighted imaging (DW)-MRI in grading Crohn's disease activity of the terminal ileum. METHODS: Three readers evaluated CE-MRI, DW-MRI, and their combinations (CE/DW-MRI and DW/CE-MRI, depending on which protocol was used at the start of evaluation). Disease severity grading scores were correlated to the Crohn's Disease Endoscopic Index of Severity (CDEIS). Diagnostic accuracy, severity grading, and levels of confidence were compared between imaging protocols and interobserver agreement was calculated. RESULTS: Sixty-one patients were included (30 female, median age 36). Diagnostic accuracy for active disease for CE-MRI, DW-MRI, CE/DW-MRI, and DW/CE-MRI ranged between 0.82 and 0.85, 0.75 and 0.83, 0.79 and 0.84, and 0.74 and 0.82, respectively. Severity grading correlation to CDEIS ranged between 0.70 and 0.74, 0.66 and 0.70, 0.69 and 0.75, and 0.67 and 0.74, respectively. For each reader, CE-MRI values were consistently higher than DW-MRI, albeit not significantly. Confidence levels for all readers were significantly higher for CE-MRI compared to DW-MRI (P < 0.001). Further increased confidence was seen when using combined imaging protocols. CONCLUSIONS: There was no significant difference of CE-MRI and DW-MRI in determining disease activity, but the higher confidence levels may favor CE-MRI. DW-MRI is a good alternative in cases with relative contraindications for the use of intravenous contrast medium.

Reliability of Measuring Ileo-Colonic Disease Activity in Crohn's Disease by Magnetic Resonance Enterography.

Background: Magnetic resonance enterography is increasingly utilized for assessment of luminal Crohn's disease activity. The Magnetic Resonance Index of Activity and the London Index are the most commonly used outcome measures in clinical trials. We assessed the reliability of these indices and several additional items. Methods: A consensus process clarified scoring conventions and identified additional items based on face validity. Four experienced radiologists evaluated 50 images in triplicate, in random order, at least 1 month apart, using a central image management system. Intra- and interrater reliability were assessed by calculating and comparing intraclass correlation coefficients. Results: Intrarater intraclass correlation coefficients (95% confidence intervals) for the Magnetic Resonance Index of Activity, London, and London "extended" indices and a visual analogue scale were 0.89 (0.84 to 0.91), 0.87 (0.83 to 0.90), 0.89 (0.85 to 0.92), and 0.86 (0.81 to 0.90). Corresponding interrater intraclass correlation coefficients were 0.71 (0.61 to 0.77), 0.67 (0.55 to 0.75), 0.70 (0.61 to 0.76), and 0.71 (0.62 to 0.77). Reliability for each index was greatest in the terminal ileum and poorest in the rectum. All 3 indices were highly correlated with the visual analogue scale; 0.79 (0.71 to 0.85), 0.78 (0.71 to 0.84), and 0.79 (0.72 to 0.85) for the Magnetic Resonance Index of Activity, London, and the London "extended" indices, respectively. Conclusions: "Substantial" interrater reliability was observed for all 3 indices. Future studies should assess responsiveness to treatment in order to confirm their utility as evaluative indices in clinical trials and clinical practice.

Serial magnetic resonance imaging for monitoring medical therapy effects in Crohn's disease.

BACKGROUND: Tumor necrosis factor (TNF) antagonists can induce mucosal healing in patients with Crohn's disease (CD), but the effects on transmural inflammation and stenotic lesions are largely unknown. METHODS: We performed a retrospective study in 50 patients (54% female, median age 37 yr) with CD who had undergone serial magnetic resonance imaging (MRI) examinations while receiving infliximab or adalimumab. Patients were grouped as clinical responders or nonresponders based on physician's assessment, laboratory, and endoscopic appearance. MRI scoring was performed by 2 radiologists in consensus blinded to clinical data using a validated MRI scoring system. In total, 64 lesions on MRI were identified for analysis. Analyses were performed using paired t test and Wilcoxon rank test. RESULTS: During anti-TNF treatment, MRI inflammation scores improved in 29 of 64 lesions (45.3%), remained unchanged in 18 of 64 lesions (28.1%), or deteriorated in 17 of 64 lesions (26.6%) over time. In the anti-TNF responder group, the mean intestinal inflammation score of all lesions improved from 5.19 to 3.12 (P < 0.0001). The mean inflammation scores in stenotic lesions in anti-TNF responders also improved significantly, from 6.33 to 4.58 (P = 0.01). In contrast, the mean inflammation scores did not change significantly (5.55-5.92, P = 0.49) in nonresponders. Diagnostic accuracy of anti-TNF response on MRI was 68%. CONCLUSIONS: Improved inflammatory activity on serial MRI scans was observed in patients with clinical response to medical therapy with anti-TNF agents in luminal CD. MRI can be used as a complementary approach to measure transmural inflammation in patients with CD and guide the optimal use of TNF antagonists in daily clinical practice.