The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer: Development and External Validation of a Preoperative Prediction Model.

Occult metastases are detected in 10-15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013-December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013-December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (n = 143, 61%), peritoneum (n = 73, 31%), or both (n = 19, 8%). The model included age (OR 1.02, 95% CI 1.00-1.03), BMI (OR 0.96, 95% CI 0.93-0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01-2.74), tumor diameter (OR 1.60, 95% CI 1.04-2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20-4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16-7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation.

The Impact of Paratracheal Lymphadenectomy on Lymph Node Yield and Short-Term Outcomes in Esophagectomy for Cancer: A Nation-Wide Propensity Score-Matched Analysis.

INTRODUCTION: The balance between potential oncological merits and surgical risks is unclear for the additional step of performing paratracheal lymphadenectomy during esophagectomy for cancer. This study aimed to investigate the impact of paratracheal lymphadenectomy on lymph node yield and short-term outcomes in patients who underwent this procedure in the Netherlands. METHODS: Patients who underwent neoadjuvant chemoradiotherapy followed by transthoracic esophagectomy were included from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). After propensity score matching Ivor Lewis and McKeown approaches separately, lymph node yield and short-term outcomes were compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. RESULTS: Between 2011 and 2017, 2,128 patients were included. Some 770 patients (n = 385 vs. n = 385) and 516 patients (n = 258 vs. n = 258) were matched for the Ivor Lewis and McKeown approaches, respectively. Paratracheal lymphadenectomy was associated with a higher lymph node yield in Ivor Lewis (23 vs. 19 nodes, p < 0.001) and McKeown (21 vs. 19 nodes, p = 0.015) esophagectomy. There were no significant differences in complications or mortality. After Ivor Lewis esophagectomy, paratracheal lymphadenectomy was associated with longer length of stay (12 vs. 11 days, p < 0.048). After McKeown esophagectomy, paratracheal lymphadenectomy was associated with more re-interventions (30% vs. 18%, p = 0.002). CONCLUSIONS: Paratracheal lymphadenectomy resulted in a higher lymph node yield but also in longer length of stay after Ivor Lewis and more re-interventions following McKeown esophagectomy.

Risk Factors for Tumor Positive Resection Margins After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: Results From the Dutch Upper GI Cancer Audit: A Nationwide Population-Based Study.

OBJECTIVE: To identify risk factors for tumor positive resection margins after neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA: Esophagectomy after nCRT is associated with tumor positive resection margins in 4% to 9% of patients. This study evaluates potential risk factors for positive resection margins after nCRT followed by esophagectomy. METHODS: All patients who underwent an elective esophagectomy following nCRT in 2011 to 2017 in the Netherlands were included. A multivariable logistic regression was performed to assess the association between potential risk factors and tumor positive resection margins. RESULTS: In total, 3900 patients were included. Tumor positive resection margins were observed in 150 (4%) patients. Risk factors for tumor positive resection margins included tumor length (in centimeters, OR: 1.1, 95% CI: 1.0-1.1), cT4-stage (OR: 3.0, 95% CI: 1.2-6.7), and an Ivor Lewis esophagectomy (OR: 1.6, 95% CI: 1.0-2.6). Predictors associated with a lower risk of tumor positive resection margins were squamous cell carcinoma (OR: 0.4, 95% CI: 0.2-0.7), distal tumors (OR: 0.5, 95% CI: 0.3-1.0), minimally invasive surgery (OR: 0.6, 95% CI: 0.4-0.9), and a hospital volume of >60 esophagectomies per year (OR: 0.6, 95% CI: 0.4-1.0). CONCLUSIONS: In this nationwide cohort study, tumor and surgical related factors (tumor length, histology, cT-stage, tumor location, surgical procedure, surgical approach, hospital volume) were identified as risk factors for tumor positive resection margins after nCRT for esophageal cancer. These results can be used to improve the radical resection rate by careful selection of patients and surgical approach and are a plea for centralization of esophageal cancer care.

Safety and feasibility of minimally invasive surgical interventions for esophageal and gastric cancer in the acute setting: a nationwide cohort study.

BACKGROUND: Minimally invasive esophagectomy and gastrectomy are increasingly performed and might be superior to their open equivalents in an elective setting. The aim of this study was to evaluate whether minimally invasive approaches can be safely applied in the acute setting as well. METHODS: All patients who underwent an acute surgical intervention for primary esophageal or gastric cancer between 2011 and 2017 were identified from the nationwide database of the Dutch Upper GI Cancer Audit (DUCA). Conversion rates, postoperative complications, re-interventions, postoperative mortality, hospital stay and oncological outcomes (radical resection rates and median lymph node yield) were evaluated. RESULTS: Between 2011 and 2017, surgery for esophagogastric cancer was performed in an acute setting in 2% (190/8861) in The Netherlands. A total of 14 acute resections for esophageal cancer were performed, which included 7 minimally invasive esophagectomies and 7 open esophagectomies. As these numbers were very low, no comparison between minimally invasive and open esophagectomies was made. A total of 122 acute resections for gastric cancer were performed, which included 39 minimally invasive gastrectomies and 83 open gastrectomies. Conversion occurred in 9 patients (23%). Minimally invasive gastrectomy was at least comparable to open gastrectomy regarding postoperative complications (36% versus 51%), median hospital stay (9 days [IQR: 7-16 days] versus 11 days [IQR: 7-17 days]), readmissions (8% versus 11%) and oncological outcomes (radical resection rate: 87% versus 66%, median lymph node yield: 21 [IQR: 15-32 days] versus 16 [IQR: 11-24 days]). CONCLUSIONS: Minimally invasive surgery for gastric cancer is safe and feasible in the acute setting, with at least comparable postoperative clinical and short-term oncological outcomes compared to open surgery but a relatively high conversion rate.

Evaluation of the Implementation of FDG-PET/CT and Staging Laparoscopy for Gastric Cancer in The Netherlands.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) has increased in the preoperative staging of gastric cancer. Dutch national guidelines have recommended the use of FDG-PET/CT and SL for patients with locally advanced tumors since July 2016. OBJECTIVE: The aim of this study was to evaluate the implementation of FDG-PET/CT and SL in The Netherlands. METHODS: Between 2011 and 2018, all patients who underwent surgery for gastric cancer were included from the Dutch Upper GI Cancer Audit. The use of FDG-PET/CT and SL was evaluated before and after revision of the Dutch guidelines. Outcomes included the number of non-curative procedures (e.g. palliative and futile procedures) and the association of FDG-PET/CT and SL, with waiting times from diagnosis to the start of treatment. RESULTS: A total of 3310 patients were analyzed. After July 2016, the use of FDG-PET/CT (23% vs. 61%; p < 0.001) and SL (21% vs. 58%; p < 0.001) increased. FDG-PET/CT was associated with additional waiting time to neoadjuvant therapy (4 days), as well as primary surgical treatment (20 days), and SL was associated with 8 additional days of waiting time to neoadjuvant therapy. Performing SL or both modalities consecutively in patients in whom it was indicated was not associated with the number of non-curative procedures. CONCLUSION: During implementation of FDG-PET/CT and SL after revision of the guidelines, both have increasingly been used in The Netherlands. The addition of these staging methods was associated with increased waiting time to treatment. The number of non-curative procedures did not differ after performing none, solely one, or both staging modalities.

Tumor volume regression during neoadjuvant chemoradiotherapy for esophageal cancer: a prospective study with weekly MRI.

Background: Neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer causes tumor regression during treatment. Tumor regression can induce changes in the thoracic anatomy, with smaller target volumes and displacement of organs at risk (OARs) surrounding the tumor as a result. Adaptation of the radiotherapy treatment plan according to volumetric changes during treatment might reduce radiation dose to the OARs, while maintaining adequate target coverage. Data on the magnitude of the volumetric changes and its impact on the thoracic anatomy is scarce. The aim of this study was to assess the volumetric changes in the primary tumor during nCRT for esophageal cancer based on weekly MRI scans.Material and methods: In this prospective study, patients with adeno- or squamous cell carcinoma of the esophagus treated with neoajduvant chemoradiotherapy according to the CROSS regimen (carboplatin + paclitaxel + 23 × 1.8 Gy) were included. Of each patient, six sequential MRI scans were acquired: one prior to nCRT, and five in each subsequent week during nCRT. Tumor volumes were delineated on the transversal T2 weighted images by two radiation oncologists. Volumetric changes were analyzed using linear mixed effects models.Results: A total of 170 MRI scans from 29 individual patients were included. The mean (± standard deviation (SD)) tumor volume at baseline was 45 cm3 (± 23). Tumor volume regression started after the first week of nCRT with a significant decrease in tumor volumes every subsequent week. A decrease to 42 cm3 (91% of initial volume), 38 cm3 (81%), 35 cm3 (77%), and 32 cm3 (72%) was observed in the second, third, fourth and fifth week of nCRT, respectively.Conclusion: Based on weekly MRI scanning during nCRT for esophageal cancer, a considerable decrease in tumor volume was observed during treatment. Volume regression and consequential anatomical changes suggest the possible benefit of adaptive radiotherapy.

Preoperative Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients With Esophageal Cancer Using 18F-FDG PET/CT and DW-MRI: A Prospective Multicenter Study.

PURPOSE: Accurate preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer could enable omission of esophagectomy in patients with a pathologic complete response (pCR). This study aimed to evaluate the individual and combined value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) during and after nCRT to predict pathologic response in patients with esophageal cancer. METHODS AND MATERIALS: In this multicenter prospective study, patients scheduled to receive nCRT followed by esophagectomy for esophageal cancer underwent 18F-FDG PET/CT and DW-MRI scanning before the start of nCRT, during nCRT, and before esophagectomy. Response to nCRT was based on histopathologic evaluation of the resection specimen. Relative changes in 18F-FDG PET/CT and DW-MRI parameters were compared between patients with pCR and non-pCR groups. Multivariable ridge regression analyses with bootstrapped c-indices were performed to evaluate the individual and combined value of 18F-FDG PET/CT and DW-MRI. RESULTS: pCR was found in 26.1% of 69 patients. Relative changes in 18F-FDG PET/CT parameters after nCRT (Δ standardized uptake value [SUV]mean,postP = .016, and Δ total lesion glycolysis postP = .024), as well as changes in DW-MRI parameters during nCRT (Δ apparent diffusion coefficient [ADC]duringP = .008) were significantly different between pCR and non-pCR. A c-statistic of 0.84 was obtained for a model with ΔADCduring, ΔSUVmean,post, and histology in classifying patients as pCR (versus 0.82 for ΔADCduring and 0.79 for ΔSUVmean,post alone). CONCLUSIONS: Changes on 18F-FDG PET/CT after nCRT and early changes on DW-MRI during nCRT can help identify pCR to nCRT in esophageal cancer. Moreover, 18F-FDG PET/CT and DW-MRI might be of complementary value in the assessment of pCR.

The Predictive Value of Low Muscle Mass as Measured on CT Scans for Postoperative Complications and Mortality in Gastric Cancer Patients: A Systematic Review and Meta-Analysis.

Risk assessment is relevant to predict outcomes in patients with gastric cancer. This systematic review aimed to investigate the predictive value of low muscle mass for postoperative complications in gastric cancer patients. A systematic literature search was performed to identify all articles reporting on muscle mass as measured on computed tomography (CT) scans in patients with gastric cancer. After full text screening, 15 articles reporting on 4887 patients were included. Meta-analysis demonstrated that patients with low muscle mass had significantly higher odds of postoperative complications (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.55-2.83) and severe postoperative complications (Clavien-Dindo grade ≥III, OR: 1.73, 95% CI: 1.14-2.63). Moreover, patients with low muscle mass had a significantly higher overall mortality (hazard ratio (HR): 1.81, 95% CI: 1.52-2.14) and disease-specific mortality (HR: 1.58, 95% CI: 1.36-1.84). In conclusion, assessment of muscle mass on CT scans is a potential relevant clinical tool for risk prediction in gastric cancer patients. Considering the heterogeneity in definitions applied for low muscle mass on CT scans in the included studies, a universal cutoff value of CT-based low muscle mass is required for more reliable conclusions.

Optimal timing for prediction of pathologic complete response to neoadjuvant chemoradiotherapy with diffusion-weighted MRI in patients with esophageal cancer.

OBJECTIVE: This study was conducted in order to determine the optimal timing of diffusion-weighted magnetic resonance imaging (DW-MRI) for prediction of pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: Patients with esophageal adenocarcinoma or squamous cell carcinoma who planned to undergo nCRT followed by surgery were enrolled in this prospective study. Patients underwent six DW-MRI scans: one baseline scan before the start of nCRT and weekly scans during 5 weeks of nCRT. Relative changes in mean apparent diffusion coefficient (ADC) values between the baseline scans and the scans during nCRT (ΔADC(%)) were compared between pathologic complete responders (pCR) and non-pCR (tumor regression grades 2-5). The discriminative ability of ΔADC(%) was determined based on the c-statistic. RESULTS: A total of 24 patients with 142 DW-MRI scans were included. pCR was observed in seven patients (29%). ΔADC(%) from baseline to week 2 was significantly higher in patients with pCR versus non-pCR (median [IQR], 36% [30%, 41%] for pCR versus 16% [14%, 29%] for non-pCR, p = 0.004). The ΔADC(%) of the second week in combination with histology resulted in the highest c-statistic for the prediction of pCR versus non-pCR (0.87). The c-statistic of this model increased to 0.97 after additional exclusion of patients with a small tumor volume (< 7 mL, n = 3) and tumor histology of the resection specimen other than adenocarcinoma or squamous cell carcinoma (n = 1). CONCLUSION: The relative change in tumor ADC (ΔADC(%)) during the first 2 weeks of nCRT is the most predictive for pathologic complete response to nCRT in esophageal cancer patients. KEY POINTS: • DW-MRI during the second week of neoadjuvant chemoradiotherapy is most predictive for pathologic complete response in esophageal cancer. • A model including ΔADCweek 2was able to discriminate between pathologic complete responders and non-pathologic complete responders in 87%. • Improvements in future MRI studies for esophageal cancer may be obtained by incorporating motion management techniques.

Radiation dose and pathological response in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery: a multi-institutional analysis.

Purpose: To explore whether a higher neoadjuvant radiation dose increases the probability of a pathological complete response (pCR) or pathological major response (pMR) response in oesophageal cancer patients. Material and methods: Between 2000 and 2017, 1048 patients from four institutions were stratified according to prescribed neoadjuvant radiation doses of 36.0 Gy (13.3%), 40.0 Gy (7.4%), 41.4 Gy (20.1%), 45.0 Gy (25.5%) or 50.4 Gy (33.7%) in 1.8-2.0 Gy fractions. Endpoints were pCR (tumour regression grade (TRG) 1) and pMR (TRG 1 + 2). Multivariable binary (TRG 1 + 2 vs. TRG > 2) and ordinal (TRG 1 vs. TRG 2 vs. TRG > 2) logistic regression analyses were performed, with subgroup analyses according to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)). Variables entered in the regression model along with neoadjuvant radiation dose were clinical tumour stage (cT), histology, chemotherapy regimen, induction chemotherapy and time from neoadjuvant chemoradiation to surgery. Results: A pCR was observed in 312 patients (29.8%); in 22.7% patients with AC and in 49.6% patients with SCC. No radiation dose-response relation was observed for pCR (OR = 1.01, 95% CI: 0.98-1.05 for AC and OR = 1.03, 95% CI: 0.96-1.10 for SCC). A pMR was observed in 597 patients (57.0%); in 53.4% patients with AC and in 67.2% patients with SCC. A higher radiation dose increased the probability of achieving pMR (OR = 1.04, 95% CI: 1.02-1.05). Factors reducing this probability were advanced cT stage (reference = cT1-2; cT3: OR = 0.54, 95% CI: 0.37-0.80; cT4: OR = 0.45, 95% CI: 0.24-0.84), AC histology (reference = SCC; OR = 0.62, 95% CI: 0.44-0.88), the use of non-platinum based chemotherapy in SCC patients (OR = 0.30, 95% CI: 0.10-0.91) and platinum based chemotherapy without induction chemotherapy in patients with AC (OR = 0.56, 95% CI: 0.42-0.76). The radiation dose-response relation was confirmed in a subgroup analysis of histologic subtypes (OR = 1.02, 95% CI: 1.01-1.04 for AC and OR = 1.05, 95% CI: 1.02-1.08 for SCC). Conclusions: Neoadjuvant radiation dose impacts pathological response in terms of pMR in oesophageal cancer patients. No radiation dose-response effect was observed for pCR. Further prospective trials are needed to investigate the dose-response relation in terms of pCR.

New-onset atrial fibrillation after esophagectomy for cancer.

Esophagectomy with en-bloc lymphadenectomy after neoadjuvant chemo(radio)therapy is the standard of care for resectable locally advanced esophageal cancer. Postoperative complications may have a significant impact on the duration of hospital stay and quality of life. Early recognition and treatment of complications may reduce failure to rescue rates and improve postoperative outcomes. New-onset atrial fibrillation (AF) after esophagectomy for cancer is frequently observed, and may be related to other postoperative complications. AF could function as an early warning sign for other complications in the postoperative course after esophagectomy and may thus be of clinical value. This review discusses the pathophysiology and possible risk factors of AF, the association between AF and other postoperative complications, and the influence of AF on postoperative outcomes after esophagectomy for cancer. Furthermore, clinical recommendations for the management of new-onset AF after esophagectomy for cancer are provided.

Frequency of surgical resection after starting neoadjuvant chemoradiotherapy in patients with esophageal cancer: A population-based cohort study.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) for resectable esophageal cancer is accompanied by the risk of treatment-related toxicity. The aim of this population-based cohort study was to provide insight in patients who do not proceed to surgical resection after starting nCRT. METHODS: Patients who started nCRT for primary esophageal cancer diagnosed in 2015 and 2016 were selected from the nationwide population-based cancer registry. Outcome measurements included omission from surgical resection, reasons for omission of surgical resection, mortality during nCRT (≤90 days after ending nCRT) and 1-year overall survival. Multivariable logistic regression analyses were performed to identify predictive factors for omission of surgical resection. RESULTS: A total of 1521 patients were included, of whom 215 (14.1%) did not undergo surgical resection after starting nCRT. Age (OR:1.04, 95%CI:1.01-1.06), BMI (OR:0.95, 95%CI:0.90-0.99), WHO performance status (WHO 1: OR:1.62, 95%CI:1.16-2.62 and WHO 2: OR:3.53, 95%CI:1.68-7.41) and clinical N status (cN2: OR:1.57, 95% CI:1.04-2.37 and cN3: OR:2.52, 95%CI:1.14-5.55) were significantly associated with omission from surgery. The most frequently reported reasons for omission from surgery were disease progression (44.3%) and physical functioning (22.8%). During nCRT or within the subsequent waiting period to surgery, 38 patients (2.5%) deceased. One year overall survival of the patients who underwent nCRT followed by surgical resection was 94.9%, and 73.5% in the patients who did not undergo surgical resection following nCRT. CONCLUSIONS: One in 7 patients who started nCRT for esophageal cancer do not proceed to surgical resection and have a decreased one year overall survival compared to patients who do proceed to surgical resection. Mortality during nCRT is considerable.

Imaging strategies in the management of gastric cancer: current role and future potential of MRI.

Accurate preoperative staging of gastric cancer and the assessment of tumor response to neoadjuvant treatment is of importance for treatment and prognosis. Current imaging techniques, mainly endoscopic ultrasonography (EUS), computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), have their limitations. Historically, the role of magnetic resonance imaging (MRI) in gastric cancer has been limited, but with the continuous technical improvements, MRI has become a more potent imaging technique for gastrointestinal malignancies. The accuracy of MRI for T- and N-staging of gastric cancer is similar to EUS and CT, making MRI a suitable alternative to other imaging strategies. There is limited evidence on the performance of MRI for M-staging of gastric cancer specifically, but MRI is widely used for diagnosing liver metastases and shows potential for diagnosing peritoneal seeding. Recent pilot studies showed that treatment response assessment as well as detection of lymph node metastases and systemic disease might benefit from functional MRI (e.g. diffusion weighted imaging and dynamic contrast enhancement). Regarding treatment guidance, additional value of MRI might be expected from its role in better defining clinical target volumes and setup verification with MR-guided radiation treatment.

Quantification of variations in intra-fraction motion of esophageal tumors over the course of neoadjuvant chemoradiotherapy based on cine-MRI.

To noninvasively quantify variation in intra-fraction motion of esophageal tumors over the course of neoadjuvant chemoradiotherapy (nCRT) using 2D cine-magnetic resonance imaging (MRI) series. Patients treated with nCRT for esophageal cancer underwent six MRI scans. Scans were acquired prior to the start of nCRT, followed by weekly MRI scans during nCRT. Cine-MRI series were acquired in the coronal and sagittal plane (≈1.6 Hz). To be able to quantify intra-fraction motion over a longer time period, a second cine-MRI series was performed after 10 min. Tumor motion was assessed in cranio-caudal (CC), anterior-posterior (AP) and left-right (LR) direction. Motion patterns were analyzed for the presence of deep inhales and tumor drift. A total of 232 cine-MRI series of 20 patients were analyzed. The largest tumor motion was found in CC direction, with a mean peak-to-peak motion of 12.7 mm (standard deviation [SD] 5.6), followed by a mean peak-to peak motion in AP direction of 3.8 mm (SD 2.0) and in LR direction of 2.7 mm (SD 1.3). The CC intra-fraction tumor motion can differ extensively between and within patients. Deep inhales were present in six of 232 scans (3%). After exclusion of these scans, mean CC peak-to-peak motion was12.3 mm (SD 5.2). Correction for tumor drift showed a further reduction to 11.0 mm (SD 4.6). Despite correction for tumor drift, a large variation in tumor motion occurred within patients during treatment. Mean tumor drift during the 10 min interval between the two series was 1.5 mm (SD 1.8), with a maximum of 11.6 mm. Intra-fraction tumor motion was found to be highly variable between and within patients with esophageal cancer over the course of nCRT. Correction for deep inhales and tumor drift reduced peak-to-peak motion. The stochastic nature of both deep inhales and tumor drift indicates that real-time tumor motion management during radiotherapy is a prerequisite to safely reduce treatment margins.

Surgical treatment of esophageal cancer in the era of multimodality management.

Over the last decades, the treatment of resectable esophageal cancer has evolved into a multidisciplinary process in which all players are essential for treatment to be successful. Medical oncologists and radiation oncologists have been increasingly involved since the implementation of neoadjuvant therapy, which has been shown to improve survival. Although esophagectomy is still considered the cornerstone of curative treatment for locally advanced esophageal cancer, it remains associated with considerable postoperative morbidity, despite promising results of minimally invasive techniques. In this light, both physical status and response to neoadjuvant therapy may be important factors for selecting patients who will benefit from surgery. Furthermore, it is important to optimize the entire perioperative trajectory: from the initial outpatient clinic visit to postoperative discharge. Enhanced recovery after surgery is increasingly recognized for esophagectomy and emphasizes perioperative aspects, such as nutrition, physiotherapy, and pain management. To date, several facets of esophageal cancer treatment remain topics of debate, such as the preferred neoadjuvant treatment, anastomotic technique, extent of lymphadenectomy, organization of postoperative care, and the role of surgery beyond locally advanced disease. Here, we describe the current and future perspectives in the surgical treatment of patients with esophageal cancer in the context of the available literature.

DW-MRI and DCE-MRI are of complementary value in predicting pathologic response to neoadjuvant chemoradiotherapy for esophageal cancer.

PURPOSE: To explore the potential benefit and complementary value of a multiparametric approach using diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) for prediction of response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. MATERIAL AND METHODS: Forty-five patients underwent both DW-MRI and DCE-MRI prior to nCRT (pre), during nCRT (week 2-3) (per) and after completion of nCRT, but prior to esophagectomy (post). Subsequently, histopathologic tumor regression grade (TRG) was assessed. Tumor apparent diffusion coefficient (ADC) and area-under-the-concentration time curve (AUC) were calculated for DW-MRI and DCE-MRI, respectively. The ability of these parameters to predict pathologic complete response (pCR, TRG1) or good response (GR, TRG ≤ 2) to nCRT was assessed. Furthermore the complementary value of DW-MRI and DCE-MRI was investigated. RESULTS: GR was found in 22 (49%) patients, of which 10 (22%) patients showed pCR. For DW-MRI, the 75th percentile (P75) ΔADCpost-pre was most predictive for GR (c-index = 0.75). For DCE-MRI, P90 ΔAUCper-pre was most predictive for pCR (c-index = 0.79). Multivariable logistic regression analyses showed complementary value when combining DW-MRI and DCE-MRI for pCR prediction (c-index = 0.89). CONCLUSIONS: Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer. Combining both modalities provides complementary information, resulting in a higher predictive value.

Role of adjuvant chemoradiotherapy after endoscopic treatment of early-stage esophageal cancer: a systematic review.

INTRODUCTION: Esophagectomy combined with lymphadenectomy is currently recommended for patients with high-risk early-stage esophageal cancer after endoscopic treatment (i.e. submucosal tumor invasion [sm2-3], presence of lymphovascular invasion and/or poor tumor differentiation) given the high risk of lymph node metastases. Unfortunately, some patients do not have the physiologic capability to endure surgery. For these patients chemoradiotherapy (CRT) following endoscopic treatment could be an alternative. The aim of this systematic review was to evaluate the evidence on the safety and efficacy of endoscopic treatment combined with CRT in patients with high-risk early-stage esophageal cancer. EVIDENCE ACQUISITION: A systematic literature search was performed to identify studies reporting on the safety and efficacy of CRT following endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in patients with esophageal cancer invading the muscularis mucosae or submucosa. Primary outcomes were locoregional recurrence (LRR), disease-free survival (DFS) and overall survival (OS). The secondary outcome was the occurrence of treatment-related adverse events. EVIDENCE SYNTHESIS: Six studies were included, comprising a total of 168 patients with early-stage esophageal cancer that underwent endoscopic treatment followed by CRT. Most studies were retrospective case series and included small numbers of patients (11 to 66). All patients had T1a(m3) or T1b(sm1-3) esophageal squamous cell carcinoma. Adjuvant treatment consisted of cisplatin and 5-fluorouracil with concurrent radiotherapy; doses ranging from 40 to 60 Gy. The overall LRR rate ranged between 0-9%. Reported 3-year DFS and OS rates ranged between 69-100% and 87-100%, respectively. In all studies ESD and/or EMR was safely performed without serious complications. The observed CRT treatment-related toxicity (grade ≥3) ranged between 0% and 32%. CONCLUSIONS: This review demonstrates that the current available literature lacks large prospective adequately powered studies and does not allow any firm conclusion regarding the role of endoscopic treatment combined with adjuvant CRT for patients with high-risk early-stage esophageal cancer.

Patient perspectives on repeated MRI and PET/CT examinations during neoadjuvant treatment of esophageal cancer.

OBJECTIVE: The perceived burden of diagnostic tests by patients during the assessment of esophageal cancer warrants attention with the current increase in repeated imaging for purposes of disease monitoring during and after treatment. The purpose of this prospective study was to evaluate the experienced burden associated with repeated MRI and positron emission tomography with integrated CT (PET/CT) examinations during neoadjuvant treatment for esophageal cancer from the perspective of the patient. METHODS: In 27 patients receiving neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer MRI and PET/CT examinations were performed before nCRT, during nCRT and before surgery. The experienced burden during repeated MRI and PET/CT examinations was evaluated with a self-report questionnaire addressing discomfort, pain, anxiety and embarrassment, each measured on a 5-point Likert scale (1 = none; up to 5 = very much). In addition, a comparative assessment was used to rank MRI, PET/CT and baseline endoscopy. RESULTS: All scans were performed without the occurrence of an adverse event. Few patients experienced discomfort (mean score ±SD: 1.9 ± 1.0 for MRI vs 2.0 ± 1.0 for PET/CT, p = 0.586), pain (1.1 ± 0.4 for MRI vs 1.3 ± 0.7 for PET/CT, p = 0.059), anxiety (1.0 ± 0.2 for MRI vs 1.0 ± 0.2 for PET/CT, p = 1.000) and embarrassment (1.0 ± 0 for MRI vs 1.0 ± 0.2 for PET/CT, p = 0.317) during both MRI and PET/CT. Patients preferred MRI over PET/CT (67% vs 22%, respectively, p = 0.023), and MRI over endoscopy (59% vs 19%, respectively, p = 0.027). In the comparison between PET/CT and endoscopy, 59% of patients preferred PET/CT and 26% preferred endoscopy (p = 0.093). CONCLUSION: Repeated imaging with both MRI and PET/CT is generally well-tolerated for the assessment of response to treatment in esophageal cancer patients. Shorter acquisition times and altered body positioning during scanning will likely improve patient experience. Advances in knowledge: This paper demonstrates that MRI and PET/CT are generally well-tolerated imaging procedures for the assessment of response to treatment in esophageal cancer patients. When asked to rank different tests, patients preferred MRI over PET/CT and endoscopy.

Generalized cardiovascular disease on a preoperative CT scan is predictive for anastomotic leakage after esophagectomy.

BACKGROUND: Recent studies demonstrated that calcification of arteries supplying the gastric tube is associated with anastomotic leakage after esophagectomy. However, it remains unclear whether this association only derives from local flow limitations, or generalized vascular disease as well. The purpose of this study was to determine whether calcification throughout the entire cardiovascular system is associated with anastomotic leakage. METHODS: Consecutive patients who underwent an esophagectomy with gastric tube reconstruction and cervical anastomosis for esophageal cancer were analyzed. Diagnostic CT images were scored for the presence of arterial calcification on 10 locations based on a visual grading system. The association with anastomotic leakage was studied using logistic regression analysis. RESULTS: A total of 406 patients were included for analysis of whom 104 developed anastomotic leakage (25.6%). Presence of calcification in the coronary arteries (minor calcification: 36.5% leakage; no calcification: 18.1%, p = .001), supra-aortic arteries (minor calcification: 30.9% leakage; major calcification: 35.3%; no calcification: 16.1%, p = .007 and p < .001, respectively) and thoracic aorta (major calcification: 33.3% leakage; no calcification: 19.4%, p = .011) was associated with leakage. In multivariable analysis, minor calcification of the coronary arteries (OR 2.29, 95% CI: 1.28-4.12, p = .005) and calcification of the supra-aortic arteries (OR 2.48, 95% CI: 1.30-4.74, p = .006 for minor calcification and OR 2.72, 95% CI: 1.49-4.99, p = .001 for major calcification) remained independently associated with leakage. CONCLUSIONS: Calcification of the coronary and supra-aortic arteries on routine CT are predictive of cervical anastomotic leakage after esophagectomy. These results suggest that generalized cardiovascular disease is a strong indicator for the risk of leakage.