Cervical ultrasonography has no additional value over negative 18F-FDG PET/CT scans for diagnosing cervical lymph node metastases in patients with oesophageal cancer.

OBJECTIVES: To investigate the additional value of cervical ultrasonography over 18F-FDG PET/CT for diagnosing cervical lymph node metastases in patients with newly diagnosed oesophageal cancer. METHODS: Between January 2013 and January 2016, 163 patients with newly diagnosed oesophageal cancer underwent both cervical ultrasonography and 18F-FDG PET/CT at a tertiary referral centre in the Netherlands. Retrospective clinical data analysis was performed to assess the diagnostic value of cervical ultrasonography and 18F-FDG PET/CT for the detection of cervical lymph node metastases. Fine needle aspiration or clinical follow-up was used as reference standard. RESULTS: The overall incidence of patients with cervical lymph node metastases was 14%. The sensitivity of 18F-FDG PET/CT to detect cervical lymph node metastases was 82% (95% CI 59-94%) and specificity was 91% (95% CI 85-95%). The sensitivity and specificity of cervical ultrasonography were 73% (95% CI 50-88%) and 84% (95% CI 77-90%), respectively. In patients with a negative 18F-FDG PET/CT, 12 of 133 (9%) patients had suspicious nodes on cervical ultrasonography. In all these 12 patients the nodes were confirmed benign. CONCLUSIONS: Cervical ultrasonography has no additional diagnostic value to a negative integrated 18F-FDG PET/CT for the detection of cervical lymph node metastases in patients with newly diagnosed oesophageal cancer. KEY POINTS: • Cervical ultrasonography has no value over PET/CT in evaluating cervical node metastases. • PET/CT provides greater diagnostic confidence compared to cervical ultrasonography. • Cervical ultrasonography during standard diagnostic work-up may be considered unnecessary. • Cervical lesions on PET/CT require cytopathological confirmation by FNA.

Endoscopic biopsy and EUS for the detection of pathologic complete response after neoadjuvant chemoradiotherapy in esophageal cancer: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Accurate determination of residual cancer status after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer could assist in selecting the optimal treatment strategy. The aim of this study was to review the evidence on the diagnostic accuracy of endoscopic biopsy and EUS after nCRT for detecting residual cancer at the primary tumor site (ypT+) and regional lymph nodes (ypN+) as opposed to a pathologic complete response (ypT0 and ypN0). METHODS: PubMed/Medline, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies reporting on the accuracy of endoscopic biopsy or EUS in detecting residual cancer versus complete response after nCRT for esophageal cancer with histopathology as the reference standard. Bivariate random-effects models were used to estimate pooled sensitivities and specificities and examine sources of heterogeneity. RESULTS: Twenty-three studies comprising 12 endoscopic biopsy studies (1281 patients), 11 EUS studies reporting on ypT status (593 patients), and 10 EUS studies reporting on ypN status (602 patients), were included. Pooled estimates for sensitivity of endoscopic biopsy after nCRT for predicting ypT+ were 34.5% (95% confidence interval [CI], 26.0%-44.1%) and for specificity 91.0% (95% CI, 85.6%-94.5%). Pooled estimates for sensitivity of EUS after nCRT were 96.4% (95% CI, 91.7%-98.5%) and for specificity were 10.9% (95% CI, 3.5%-29.0%) for detecting ypT+, and 62.0% (95% CI, 46.0%-75.7%) and 56.7% (95% CI, 41.8%-70.5%) for detecting ypN+, respectively. CONCLUSIONS: Endoscopic biopsy after nCRT is a specific but not sensitive method for detecting residual esophageal cancer. Although EUS after nCRT yields a high sensitivity, only a limited number of patients will have negative findings at EUS with still a substantial false-negative rate. Furthermore, EUS provides only moderate accuracy for detecting residual lymph node involvement. Based on these findings, these endoscopic modalities cannot be used to withhold surgical treatment in test-negative patients after nCRT. ( CLINICAL TRIAL REGISTRATION NUMBER: CRD42015016527.).

The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program.

BACKGROUND: Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. METHODS: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months. RESULTS: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03). CONCLUSIONS: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.

Limited additional value of cervical ultrasonography over a negative 18F-FDG PET/CT for diagnosing cervical lymph node metastases in patients with esophageal cancer: a systematic review and meta-analysis.

OBJECTIVE: To assess the additional value of cervical ultrasonography as supplement to a negative fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) for detecting cervical lymph node metastases during the initial staging of patients with esophageal cancer. METHODS: PubMed/Medline, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies describing the accuracy of cervical ultrasonography and integrated F-FDG PET/CT or standalone F-FDG PET and CT for detecting cervical lymph node metastases in patients with esophageal cancer. The reference standard consisted of cytopathology and/or clinical follow-up. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of the included studies. A random effects model was used to meta-analyze the additional diagnostic value of cervical ultrasonography. RESULTS: Four diagnostic studies were eligible and included for meta-analysis, comprising 567 patients with esophageal cancer who underwent diagnostic workup before treatment. The quality of the included studies was considered reasonable; there were few concerns regarding risk of bias and applicability. In three of the four studies, cervical ultrasonography did not detect cervical lymph node metastases in addition to a negative finding on F-FDG PET/CT or standalone F-FDG PET and CT. In one study, cervical ultrasonography detected additional cervical lymph node metastases in 4% (3/74) of patients over standalone F-FDG PET and CT. Pooled estimate of the additional value of cervical ultrasonography was 1% (95% confidence interval: 0-5%). CONCLUSION: Cervical ultrasonography has very limited additional diagnostic value as supplement to a negative F-FDG PET/CT in the detection of cervical lymph node metastases during the initial staging of patients with esophageal cancer.

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.