R. S. Gillies

Additional benefit of 18F-fluorodeoxyglucose integrated positron emission tomography/computed tomography in the staging of oesophageal cancer

Objective18F-fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to improve the accuracy of staging in oesophageal cancer. We assessed the benefit of PET/CT over conventional staging and determined if tumour histology had any significant impact on PET/CT findings.MethodsA retrospective cohort study, reviewing the results from 200 consecutive patients considered suitable for radical treatment, undergoing routine PET/CT staging comparing the results from CT and endoscopic ultrasound, as well as multi-disciplinary team records. Adenocarcinoma and squamous cell carcinoma were compared for maximum Standardised Uptake Value (SUVmax), involvement of local lymph nodes and distant metastases.ResultsPET/CT provided additional information in 37 patients (18.5%) and directly altered management in 34 (17%): 22 (11%) were upstaged; 15 (7.5%) were downstaged, 12 of whom (6%) received radical treatment. There were 11 false negatives (5.5%) and 1 false positive (0.5%). SUVmax was significantly lower for adenocarcinoma than squamous cell carcinoma (median 9.1 versus 13.5, pu2009=u20090.003).ConclusionsStaging with PET/CT offers additional benefit over conventional imaging and should form part of routine staging for oesophageal cancer. Adenocarcinoma and squamous cell carcinoma display significantly different FDG-avidity.

Role of positron emission tomography-computed tomography in predicting survival after neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma.

Positron emission tomography combined with computed tomography (PET–CT) is increasingly being used in the staging of oesophageal cancer. Some recent reports suggest it may be used to predict survival. None of these studies, however, reported on the prognostic value of PET–CT performed before neoadjuvant chemotherapy and surgery. The aim of this study was to determine whether pretreatment PET–CT could predict survival.

Nonoperative Management of Appendicitis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Received July 27, 2016; Revised September 13, 2016; Acce 13, 2016. From the Oxford OesophagoGastric Centre, Churchill Hos Kafsi, Gillies, Maynard) and the Department of Emergenc Radcliffe Hospital (Hammer, Gilmour), Oxford University Foundation Trust; and NIHR Oxford Biomedical Resear dlay), Churchill Hospital, Oxford, UK. Correspondence address: John M Findlay, BMedSci, MRCS; Oxford OesophagoGastric Centre, Churchill H OX3 7LJ, UK. email: john.findlay@oncology.ox.ac.uk

The effect of formalizing enhanced recovery after esophagectomy with a protocol.

Enhanced recovery after surgery (ERAS) pathways aim to accelerate functional return and discharge from hospital. They have proven effective in many forms of surgery, most notably colorectal. However, experience in esophagectomy has been limited. A recent study reported significant reductions in pulmonary complications, mortality, and length of stay following the introduction of an ERAS protocol alone, without the introduction of any clinical changes. We instituted a similar change 16 months ago, introducing a protocol to provide a formal framework, for our existing postoperative care. This retrospective analysis compared outcome following esophagectomy for the 16 months before and 20 months after this change. Data were collected from prospectively maintained secure web-based multidisciplinary databases. Complication severity was classified using the Clavien-Dindo scale. Operative mortality was defined as death within 30 days of surgery, or at any point during the same hospital admission. Lower respiratory tract infection was defined as clinical evidence of infection, with or without radiological signs. Respiratory complications included lower respiratory tract infection, pleural effusion (irrespective of drainage), pulmonary collapse, and pneumothorax. Statistical analysis was performed using SPSS v21. One hundred thirty-two patients underwent esophagectomy (55 protocol group; 77 before). All were performed open. There were no differences between the two groups in terms of age, gender, operation, use of neoadjuvant therapy, cell type, stage, tumor site, or American Society of Anesthesiologists grade. Median length of stay was 14.0 days (protocol) compared with 12.0 before (interquartile range 9-19 and 9.5-15.5, respectively; P = 0.073, Mann-Whitney U-test). Readmission within 30 days of discharge occurred in five (9.26%) and six (8.19%; P = 1.000, Fishers exact test). There were four in-hospital deaths (3.03%): one (1.82%) and three (3.90%), respectively (P = 0.641). There were no differences in the severity of complications (P = non-significant; Pearsons chi-squared). There were no differences in the type of complications occurring in either group. The protocol was completed successfully by 26 (47.3%). No baseline factors were predictive of this. In contrast to previous studies, we did not demonstrate any improvement in outcome by formalizing our existing pathway using a written protocol. Consequently, improvements in short-term outcome from esophagectomy within ERAS would seem to be primarily due to improvements in components of perioperative care. Consequently, we would recommend that centers introducing new (or reviewing existing) ERAS pathways for esophagectomy focus on optimizing clinical aspects of such standardized pathways.

Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer

AbstractObjectivesReports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial.MethodsConsecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24–28xa0days after the start of cycle 2.ResultsForty-eight subjects were included: mean age 65xa0years; 37 male. Using the median percentage reduction in SUVmax (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; Pu2009=u20090.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; Pu2009=u20090.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect.ConclusionsThere was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low.Key Points• PET/CT may predict tumour response to chemotherapy in oesophageal cancer.n • This was a prospective study using a standardised chemotherapy regimen.n • A significant association between PET/CT findings and disease response was found.n • However accuracy in predicting pathological response was relatively low.

Left thoracoabdominal esophagectomy: results from a single specialist center.

The left thoracoabdominal approach to esophagectomy is not widely performed, despite offering excellent exposure to tumors of the esophagogastric junction. Criticisms of the approach have focused on historically high rates of mortality, complications, and positive resection margins. Our aim was to determine whether left thoracoabdominal esophagectomy could combine a radical oncological resection with acceptably low mortality and morbidity. A retrospective cohort study of all left thoracoabdominal esophagectomies was performed at a single specialist center over an 11-year period. Primary outcomes were in-hospital mortality, complications, resection margin involvement, and lymph node yield; secondary outcomes were 1-year and 5-year survival. Two hundred eleven esophagectomies were performed. In-hospital mortality was 5.7% (12/211). One hundred one subjects (47.9%) had an uncomplicated recovery; 110 subjects (52.1%) developed at least one complication. There were 15 clinically significant anastomotic leaks (7.1%). Twenty-four subjects (11.4%) required emergency reoperation, the most common indication being anastomotic leakage. Complete tumor excision (R0 resection) was achieved in 151 of 211 cases (71.6%); median lymph node yield was 24. One-year and 5-year survival rates were 70% (147/211) and 21% (24/116), respectively. Left thoracoabdominal esophagectomy can combine a radical oncological resection with acceptably low mortality and morbidity.

Restaging oesophageal cancer after neoadjuvant therapy with 18 F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery

AbstractObjectivesIt is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk.MethodsThis was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by 18F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014).ResultsThree hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91xa0%) and PET-CT in 17 (6.07xa0%). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1xa0%). PET-CT was more sensitive than CT (pu2009=u20090.005, McNemar’s test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0xa0%; both risk factors), medium (22.4xa0%; either), and low risk (3.87xa0%; neither) groups (pu2009<u20090.001). Decision theory supported restaging PET-CT.ConclusionsPET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply.Key Points• Restaging18F-FDG-PET-CT after neoadjuvant chemotherapy identifies metastases in 6xa0% of patientsn • Restaging18F-FDG-PET-CT is more sensitive than CT for detecting interval progressionn • Despite this, at surgery 10xa0% of patients had unsuspected incurable diseasen • New concepts (FDG-avid nodal stage and response) plus tumour impassability stratify riskn • Higher risk (if not all) patients may benefit from additional restaging modalities

Attempted validation of the NUn score and inflammatory markers as predictors of esophageal anastomotic leak and major complications

The ability to predict complications following esophagectomy/extended total gastrectomy would be of great clinical value. A recent study demonstrated significant correlations between anastomotic leak (AL) and numerical values of C-reactive protein (CRP), white cell count (WCC) and albumin measured on postoperative day (POD) 4. A predictive model comprising all three (NUn score >10) was found to be highly sensitive and discriminant in predicting AL and complications. We attempted a retrospective validation in our center. Data were collected on all resections performed during a 5-year period (April 2008-2013) using prospectively maintained databases. Our biochemistry laboratory uses a maximum CRP value (156 mg/L), unlike that of the original study; otherwise all variables and outcome measures were comparable. Analysis was performed for all patients with complete blood results on POD4. Three hundred twenty-six patients underwent resection, of which 248 had POD4 bloods. There were 21 AL overall (6.44%); 16 among those with complete POD4 blood results (6.45%). There were 8 (2.45%) in-hospital deaths; 7 (2.82%) in those with POD4 results. No parameters were associated with AL or complication severity on univariate analysis. WCC was associated with AL in multivariate binary logistic regression with albumin and CRP (OR 1.23 [95% CI 1.03-1.47]; P = 0.021). When a binary variable of CRP ≥ 156 mg/L was used rather than an absolute value, no factors were significant. Mean NUn was 8.30 for AL, compared with 8.40 for non-AL (P = 0.710 independent t-test). NUn > 10 predicted 0 of 16 leaks (sensitivity 0.00%, specificity 94.4%, receiver operator curve [ROC] area under the curve [AUC] 0.485; P = 0.843). NUn > 7.65 was 93% sensitive and 21.6% specific. ROC for WCC alone was comparable with NUn (AUC 0.641 [0.504-0.779]; P = 0.059; WCC > 6.89 93.8% sensitive, 20.7% specific; WCC > 15 6.3% sensitive and 97% specific). There were no associations between any parameters and other complications. In a comparable cohort with the original study, we demonstrated a similar multivariate association between WCC alone on POD4 and subsequent demonstration of AL, but not albumin or CRP (measured up to 156 mg/L). The NUn score overall (calculated with this caveat) and a threshold of 10 was not found to have clinical utility in predicting AL or complications.

Individual risk modelling for esophagectomy: a systematic review.

IntroductionA number of models have been applied to predict outcomes from esophagectomy. This systematic review aimed to compare their clinical credibility, methodological quality and performance.MethodsA systematic review of the PubMed, EMBASE and Cochrane databases was performed in October 2012. Model and study quality were appraised using the framework of Minne et al.ResultsTwenty studies were included in total; these were heterogeneous, retrospective and conducted over a number of years; all models were generated via logistic regression. Overall mortality was high, and consequently not representative of current practice. Clinical credibility and methodological quality were variable, with frequent failure to perform internal validation and variable presentation of calibration and discrimination metrics. P-POSSUM demonstrated the best calibration and discrimination for predicting mortality. Other than the Southampton score (which has yet to be externally validated) and the Amsterdam score, no studies had utility in predicting complications.ConclusionWhilst a number of models have been developed, adapted or trialled, due to numerous limitations, larger and more contemporary studies are required to develop and validate models further. The role of alternative techniques such as decision tree analysis and artificial neural networks is not known.

Metabolic nodal response as a prognostic marker after neoadjuvant therapy for oesophageal cancer

The ability to predict recurrence and survival after neoadjuvant chemotherapy (NAC) and surgery for oesophageal cancer remains elusive. This study evaluated the role of [18F]fluorodeoxyglucose (FDG) PET–CT in assessing tumour and nodal response as a prognostic marker.