P.S.N. Van Rossum

Imaging of oesophageal cancer with FDG-PET/CT and MRI

Integrated 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that have current and future potential to overcome important limitations of conventional staging methods in the management of patients with oesophageal cancer. PET/CT has emerged as an important part of the standard work-up of patients with oesophageal cancer. Besides its important ability to detect unsuspected metastatic disease, PET/CT may be useful in the assessment of treatment response, radiation treatment planning, and detection of recurrent disease. In addition, high-resolution T2-weighted MRI and DWI have potential complementary roles. Recent improvements in MRI protocols and techniques have resulted in better imaging quality with the potential to bring improvement in staging, radiation treatment planning, and the assessment of treatment response. Optimal use and understanding of PET/CT and MRI in oesophageal cancer will contribute to the impact of these advancing technologies in tailoring treatment to the individual patient and achieving best possible outcomes. In this article, we graphically outline the current and potential future roles of PET/CT and MRI in the multidisciplinary management of oesophageal cancer.

Radiofrequency ablation of small breast tumours: evaluation of a novel bipolar cool-tip application.

BACKGROUND Although radiofrequency ablation (RFA) is promising for the local treatment of breast cancer, burns are a frequent complication. The safety and efficacy of a new technique with a bipolar RFA electrode was evaluated. METHODS Dosimetry was assessed ex vivo in bovine mammary tissue, applying power settings of 5-15 W with 10-20 min exposure and 3.0-12.0 kJ to a 20-mm active length bipolar internally cooled needle-electrode. Subsequently, in 15 women with invasive breast carcinoma ≤2.0 cm diameter ultrasound-guided RFA was performed followed by immediate resection. RESULTS An ablation zone of 2.5 cm was reached in the ex vivo experiments at 15 W at 9.0 kJ administered energy. Histopathology revealed complete cell death in 10 of 13 patients (77%); in 3 patients partial ablation was due to inaccurate probe positioning. In 1 patient a pneumothorax was caused by the probe placement, treated conservatively. No burns occurred. CONCLUSIONS Ultrasound-guided RFA with a bipolar needle-electrode appears to be a safe local treatment technique for invasive breast cancer up to 2 cm. Ways to improve placement of the probe and direct monitoring of the ablation-effect should be the aim of further research.

The peri‐esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri‐esophageal fascias have not been described and it is unclear whether this layer can be visualized by non‐invasive imaging. This study aimed to provide a comprehensive description of the peri‐esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2‐weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri‐esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion‐triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named ‘aorto‐esophageal ligament’ and the layer connecting aorta to the right pleural reflection ‘aorto‐pleural ligament’. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named ‘peri‐esophageal compartment’ and the posterior compartment ‘para‐aortic compartment’. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long‐standing paradigm that no such structure exists. A comprehensive, detailed description of the peri‐esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI.

Long-term quality of life after oesophagectomy with gastric conduit interposition for cancer

BACKGROUND Gaining insight in long-term health-related quality of life more than 1year after oesophagectomy will assist clinical decision-making and inform patients about the long-term consequences of surgery. METHODS In this cross-sectional study, all consecutive patients who underwent oesophageal resection with gastric interposition for cancer at a tertiary referral centre between January 2007 and July 2012 were included. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and QLQ-OES18 were sent to all patients alive without recurrence more than 1year after surgery. RESULTS The questionnaires were completed by 92 of 100 patients. Median duration of follow-up after surgery at completing the questionnaire was 36months (range: 12-75). Global quality of life scores were similar to a general population reference group (76±19 versus 78±17; p=0.26). However, patients scored significantly worse compared to the general population reference group on physical-, role-, cognitive- and social functioning (p<0.001). Neoadjuvant therapy and minimally invasive oesophagectomy were associated with significantly better health-related quality of life (HRQL) and symptom scores (p<0.05). CONCLUSION Global HRQL more than 1year after oesophagectomy with gastric tube reconstruction is comparable to the general Dutch background population, while specific functional and symptom scores are significantly worse. Neoadjuvant therapy and minimally invasive surgery are associated with quality of life benefits in long-term survivors.

Impact of Weekday of Esophagectomy on Short-term and Long-term Oncological Outcomes: A Nationwide Population-based Cohort Study in the Netherlands.

Objective: The aim of this study was to determine whether weekday of esophagectomy impacts 30-day mortality, and short- and long-term oncologic outcomes in esophageal cancer. Summary of background data: Recent literature suggests a relationship between the weekday of esophagectomy and overall survival. This finding could impact clinical practice, but has not yet been validated in other studies. Methods: The Netherlands Cancer Registry database (2005–2013) identified all patients who underwent esophagectomy for esophageal cancer. The impact of weekday on 30-day mortality, the total number of resected lymph nodes, and R0 resection rates was evaluated with multivariable logistic regression analyses and for overall survival with Cox regression analyses. Results: In total, 3840 patients were included. Weekday was not significantly associated with 30-day mortality (P > 0.05), nor the total number of resected lymph nodes (P > 0.05), nor with R0 resection rates (P > 0.05). Also, weekday did not significantly influence overall survival using weekday as discrete variable [Monday–Friday, hazard ratio (HR) 0.98, P = 0.140), as 2 weekday categories (Wednesday–Friday vs Monday–Tuesday, HR 0.97, P = 0.434), or with separate weekday categories (Tuesday vs Monday, HR 0.99, P = 0.826; Wednesday vs Monday, HR 1.06, P = 0.430; Thursday vs Monday, HR 0.92, P = 0.206; Friday vs Monday, HR 0.91, P = 0.140). Conclusions: This large population-based cohort study in the Netherlands refutes the finding from a previous report that suggests that the weekday of esophagectomy in patients diagnosed with potentially curable esophageal cancer impacts overall survival. In addition, this study demonstrates that weekday of esophagectomy does not influence other outcomes including the 30-day mortality, total number of resected lymph nodes, and R0 resection rates.

Postoperative pain management after esophagectomy: a systematic review and meta-analysis

Effective pain management after esophagectomy is essential for patient comfort, early recovery, low surgical morbidity, and short hospitalization. This systematic review and meta-analysis aims to determine the best pain management modality focusing on the balance between benefits and risks. Medline, Embase, and the Cochrane library were systematically searched to identify all studies investigating different pain management modalities after esophagectomy in relation to primary outcomes (postoperative pain scores at 24 and 48 hours, technical failure, and opioid consumption), and secondary outcomes (pulmonary complications, nausea and vomiting, hypotension, urinary retention, and length of hospital stay). Ten studies investigating systemic, epidural, intrathecal, intrapleural and paravertebral analgesia involving 891 patients following esophagectomy were included. No significant differences were found in postoperative pain scores between systemic and epidural analgesia at 24 (mean difference (MD) 0.89; 95% confidence interval (CI) -0.47-2.24) and 48 hours (MD 0.15; 95%CI -0.60-0.91), nor described for systemic and other regional analgesia. Also, no significant differences in pulmonary complication rates were identified between systemic and epidural analgesia (relative risk (RR) 1.69; 95%CI 0.86-3.29), or between systemic and paravertebral analgesia (RR 1.49; 95%CI 0.31-7.12). Technical failure ranged from 17% to 22% for epidural analgesia. Sample sizes were too small to draw inferences on opioid consumption, the risk of nausea and vomiting, hypotension, urinary retention, and length of hospital stay when comparing the different pain management modalities including systemic, epidural, intrathecal, intrapleural, and paravertebral analgesia. This systematic review and meta-analysis shows no differences in postoperative pain scores or pulmonary complications after esophagectomy between systemic and epidural analgesia, and between systemic and paravertebral analgesia. Further randomized controlled trails are warranted to determine the optimal pain management modality after esophagectomy.

Defining pneumonia after esophagectomy for cancer: validation of the Uniform Pneumonia Score in a high volume center in North America

Surgery is a central component of multimodality therapy for esophageal and gastroesophageal junction cancer. Pneumonia is a common sequela of esophagectomy, leading to an increase in intensive care unit stay, hospital stay, readmission rates, and postoperative mortality. Developing strategies to reduce pneumonia after esophagectomy is hampered by the absence of a standardized methodology for defining pneumonia. This study aims to validate the Uniform Pneumonia Score (UPS) in a high volume center in the USA. The UPS was developed to define pneumonia after esophagectomy for cancer and is based on the assessment of temperature (°C), leukocyte count (×109/L), and pulmonary radiography. The UPS has been validated utilizing a prospective, Institutional Review Board approved database of esophageal cancer patients treated in a high volume esophagectomy center in the USA between 2010 and 2015. One hundred ninety-three consecutive patients were included and 21 (10.9%) were treated for pneumonia. The UPS was able to predict treatment for suspected pneumonia with a good sensitivity (85.7%, confidence interval (CI): 63.7%-96.7%), specificity (97.1%, CI: 93.4%-99.1%), positive predictive value (78.3%, CI: 59.9%-89.7%), and negative predictive value (98.2%, CI: 95.1%-99.4%). The diagnostic accuracy was 95.9%, CI: 92.0%-98.2%. The UPS demonstrated to be a reliable scoring system to define pneumonia after esophagectomy for cancer. Global application of this model will standardize the definition of pneumonia after esophagectomy. This will improve outcome reporting and comparisons of complications between individual institutions, clinical trials, and national audits.

Detection of distant interval metastases after neoadjuvant therapy for esophageal cancer with 18F-FDG PET(/CT): a systematic review and meta-analysis

Restaging after neoadjuvant therapy aims to reduce the number of patients undergoing esophagectomy in case of distant (interval) metastases. The aim of this study is to systematically review and meta-analyze the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and 18F-FDG PET/CT for the detection of distant interval metastases after neoadjuvant therapy in patients with esophageal cancer. PubMed/MEDLINE, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies reporting on the detection of distant interval metastases with 18F-FDG PET(/CT) in patients with esophageal cancer who received neoadjuvant therapy and both baseline staging and restaging after neoadjuvant therapy with 18F-FDG PET(/CT) imaging. The primary outcome measure was the proportion of patients in whom distant interval metastases were detected by 18F-FDG PET(/CT) as confirmed by pathology or clinical follow-up (i.e. true positives). The secondary outcome measure was the proportion of patients in whom 18F-FDG PET(/CT) restaging was false positive for distant interval metastases (i.e. false positives). Risk of bias and applicability concerns were assessed using the QUADAS-2 tool. Random-effect models were used to estimate pooled outcomes and examine potential sources of heterogeneity. Fourteen studies were included comprising a total of 1,110 patients who received baseline staging with 18F-FDG PET(/CT) imaging of whom 1,001 (90%) underwent restaging with 18F-FDG PET(/CT) imaging. Studies were generally of moderate quality. The pooled proportion of patients in whom true distant interval metastases were detected by 18F-FDG PET(/CT) restaging was 8% (95% confidence interval [CI]: 5-13%). The pooled proportion of patients in whom false positive distant findings were detected by 18F-FDG PET(/CT) restaging was 5% (95% CI: 3-9%). In conclusion,18F-FDG PET(/CT) restaging after neoadjuvant therapy for esophageal cancer detects true distant interval metastases in 8% of patients. Therefore, 18F-FDG PET(/CT) restaging can considerably impact on treatment decision-making. However, false positive distant findings occur in 5% of patients at restaging with 18F-FDG PET(/CT), underlining the need for pathological confirmation of suspected lesions.

Gross tumour delineation on Computed Tomography and Positron Emission Tomography-Computed Tomography in oesophageal cancer: a nationwide study

Background and purpose Accurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control in oesophageal cancer patients. Therefore, the aim was to assess delineation variability of the gross tumour volume (GTV) between CT and combined PET-CT in oesophageal cancer patients in a multi-institutional study. Materials and methods Twenty observers from 14 institutes delineated the primary tumour of 6 cases on CT and PET-CT fusion. The delineated volumes, generalized conformity index (CIgen) and standard deviation (SD) in position of the most cranial/caudal slice over the observers were evaluated. For the central delineated region, perpendicular distance between median surface GTV and each individual GTV was evaluated as in-slice SD. Results After addition of PET, mean GTVs were significantly smaller in 3 cases and larger in 1 case. No difference in CIgen was observed (average 0.67 on CT, 0.69 on PET-CT). On CT cranial-caudal delineation variation ranged between 0.2 and 1.5 cm SD versus 0.2 and 1.3 cm SD on PET-CT. After addition of PET, the cranial and caudal variation was significantly reduced in 1 and 2 cases, respectively. The in-slice SD was on average 0.16 cm in both phases. Conclusion In some cases considerable GTV delineation variability was observed at the cranial-caudal border. PET significantly influenced the delineated volume in four out of six cases, however its impact on observer variation was limited.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study

BackgroundNearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR.MethodsThe PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival.DiscussionIf the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped.Trial registrationThe article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341.