OBJECTIVE:This article aims to provide the first systematic review of enhanced recovery after surgery (ERAS) programs for esophagectomy and generate guidelines.
BACKGROUND:ERAS programs use ...multimodal approaches to reduce complications and accelerate recovery. Although ERAS is well established in colorectal surgery, experience after esophagectomy has been minimal. However, esophagectomy remains an extremely high-risk operation, commonly performed in patients with significant comorbidities. Consequently, ERAS may have a significant role to play in improving outcomes. No guidelines or reviews have been published in esophagectomy.
METHODS:We undertook a systematic review of the PubMed, EMBASE, and the Cochrane databases in July 2012. The literature was searched for descriptions of ERAS in esophagectomy. Components of successful ERAS programs were determined, and when not directly available for esophagectomy, extrapolation from related evidence was made. Graded recommendations for each component were then generated.
RESULTS:Six retrospective studies have assessed ERAS for esophagectomy, demonstrating favorable morbidity, mortality, and length of stay. Methodological quality is, however, low. Overall, there is little direct evidence for components of ERAS, with much derived from nonesophageal thoracoabdominal surgery.
CONCLUSIONS:ERAS in principle seems logical and safe for esophagectomy. However, the underlying evidence is poor and lacking. Despite this, a number of recommendations for practice and research can be made.
Background
Chyle leaks following oesophagectomy are a frustrating complication of surgery with considerable morbidity. The use of near infra-red (NIR) fluorescence in surgery is an emerging ...technology and the use of fluorescence to identify the thoracic duct has been demonstrated in animal work and early human case reports. This study evaluated the use mesenteric and enteral administration of indocyanine green (ICG) in humans to identify the thoracic duct during oesophagectomy.
Methods
Patients undergoing oesophagectomy were recruited to the study. Administration of ICG via an enteral route or mesenteric injection was evaluated. Fluorescence was assessed using a NIR fluorescence enabled laparoscope system with a visual scoring system and signal to background ratios. Visualisation of the thoracic duct under white light and NIR fluorescence was compared as well as any identification of active chyle leak. Patients were followed up post-operatively for adverse events and chyle leak.
Results
20 patients received ICG and were included in the study. The enteral route failed to fluoresce the thoracic duct. Mesenteric injection (17 patients) identified the thoracic duct under fluorescence prior to white light in 70% of patients with a mean signal to background ratio of 5.35. In 6 participants, a possible active chyle leak was identified under fluorescence with 4 showing active chyle leak from what was identified as the thoracic duct.
Conclusion
This study demonstrates that ICG administration via mesenteric injection can highlight the thoracic duct during oesophagectomy and may be a potential technology to reduce chyle leak following surgery.
Clinical trial registration
Clinical trials.gov (NCT03292757).
How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant ...chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful.
Oesophageal perforations and post-oesophagectomy anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a novel treatment strategy with the potential ...to promote healing and ameliorate sepsis. Only two cases of its use have been reported in the UK in the management of oesophageal wall defects, representing a limited aetiological and demographic spectrum.
From May to December 2019, 7 patients aged 27-85 years underwent EVT for disparate oesophageal wall defects. Data regarding technical success and feasibility were analysed.
Complete defect resolution was achieved in six cases (86%), requiring median of 13 days of treatment (range 6-23), and necessitating three replacement procedures (range 1-4). Significant improvement in C-reactive protein was achieved in all patients undergoing treatment (p = .015). No severe complications occurred that resulted directly from sponge placement, however two individuals (33%) developed oesophageal stricture necessitating endoscopic balloon dilatation, and one died whilst undergoing treatment.
In selected patients EVT is a safe, valuable tool for the management of a spectrum of oesophageal wall defects, with the potential to reduce associated morbidity and mortality. While this work significantly expands upon the UK reported experience of EVT, we outline the requirement for a national, prospective registry of EVT use in oesophageal leaks and perforations.
AL: anastomotic leak; CRP: C-reactive protein; CT: computed tomography; EVT: endoscopic vacuum therapy; HES: hospital episode statistics; OGD: oesophago-gastro-duodenoscopy; SEMS: oesophageal stenting with self-expanding stents; UK: United Kingdom
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Objectives
We recently described metabolic nodal stage (mN) and response (mNR) of cancer of the esophagus and gastro-esophageal junction (GEJ) to neoadjuvant chemotherapy (NAC) using
18
F-FDG PET-CT ...as new markers of disease progression, recurrence, and death. We aimed to validate our findings.
Methods
Our validation cohort comprised all patients consecutive to our discovery cohort, staged before and after NAC using PET-CT from 2014 to 2017. Multivariate binary logistic and Cox regression were performed.
Results
Fifty-one of the 200 patients had FDG-avid nodes after NAC (25.5%; i.e., lack of complete mNR), and were more likely to progress during NAC to incurable disease on PET-CT or at surgery: odds ratio 3.84 (1.46–10.1;
p
= 0.006). In 176 patients undergoing successful resection, patients without complete mNR had a worse prognosis: disease-free survival hazard ratio 2.46 (1.34–4.50);
p
= 0.004. These associations were independent of primary tumor metabolic, pathological response, and stage. In a hybrid pathological/metabolic nodal stage, avid nodal metastases conferred a worse prognosis than non-avid metastases. Lack of complete mNR predicted recurrence or death at 1 and 2 years: positive predictive values 44.4% (31.7–57.8) and 74.1% (56.6–86.3) respectively.
Conclusions
This study provides temporal validation for mNR as a new and independent predictive and prognostic marker of esophageal and GEJ cancer treated with NAC and surgery, although external validation is required to assess generalizability. mNR may provide surrogate information regarding the phenotype of metastatic cancer clones beyond the mere presence of nodal metastases, and might be used to better inform patients, risk stratify, and personalize management, including adjuvant therapy.
Key Points
• We previously described metabolic nodal response (mNR) of esophageal cancer to neoadjuvant chemotherapy using
18
F-FDG PET-CT as a predictor of unresectable disease, early recurrence, and death.
• We report the first validation of these findings. In an immediately consecutive cohort, we found consistent proportions of patients with and without mNR, and associations with abandoned resection, early recurrence, and death.
• This supports mNR as a new and actionable biomarker in esophageal cancer. Although external validation is required, mNR may provide surrogate information about the chemosensitivity of metastatic subclones, and the means to predict treatment success, guide personalized therapy, and follow-up.
Only a minority of esophageal cancers demonstrates a pathologic tumor response (pTR) to neoadjuvant chemotherapy (NAC).
F-FDG PET/CT is often used for restaging after NAC and to assess response. ...Increasingly, it is used during therapy to identify unresponsive tumors and predict pTR, using avidity of the primary tumor alone. However, definitions of such metabolic tumor response (mTR) vary. We aimed to comprehensively reevaluate metabolic response assessment using accepted parameters, as well as novel concepts of metabolic nodal stage (mN) and metabolic nodal response (mNR).
This was a single-center retrospective U.K. cohort study. All patients with esophageal cancer staged before NAC with PET/CT and after with CT or PET/CT and undergoing resection from 2006 to 2014 were identified. pTR was defined as Mandard tumor regression grade 1-3; imaging parameters included metrics of tumor avidity (SUV
), composites of avidity and volume (including metabolic tumor volume), nodal SUV
, and our new concepts of mN stage and mNR.
Eighty-two (27.2%) of 301 patients demonstrated pTR. No pre-NAC PET parameters predicted pTR. In 220 patients restaged by PET/CT, the optimal tumor ΔSUV
threshold was a 77.8% reduction. This was as sensitive as the current PERCIST 30% reduction, but more specific with a higher negative predictive value (P < 0.001). ΔSUV
and Δlength independently predicted pTR, and composite avidity/spatial metrics outperformed avidity alone. Although both mTR and mNR were associated with pTR, in 82 patients with
F-FDG-avid nodes before NAC we observed mNR in 10 (12.2%) not demonstrating mTR.
Current definitions of metabolic response are suboptimal and too simplistic. Composite avidity/volume measures improve prediction. mNR may further improve response assessment, by specifically assessing metastatic tumor subpopulations, likely responsible for disease relapse, and should be urgently assessed when considering aborting therapy on the basis of mTR alone.
Abstract
Background
Jejunal feeding is an invaluable method by which to improve the nutritional status of patients undergoing neoadjuvant and surgical treatment of oesophageal malignancies. However, ...the insertion of a feeding jejunostomy can cause significant postoperative morbidity. The aim of this study is to compare the outcomes of patients undergoing placement of feeding jejunostomy by conventional laparotomy with an alternative laparoscopic approach.
Methods
A retrospective review of data prospectively collected at the Oxford Oesophagogastric Centre between August 2017 and July 2019 was performed including consecutive patients undergoing feeding jejunostomy insertion.
Results
In the study period, 157 patients underwent jejunostomy insertion in the context of oesophageal cancer therapy, 126 (80%) by open technique and 31 (20%) laparoscopic. Pre-operative demographic and nutritional characteristics were broadly similar between groups. In the early postoperative period jejunostomy-associated complications were noted in 54 cases (34.4%) and were significantly more common among those undergoing open as compared with laparoscopic insertion (38.1% vs. 19.3%, P = 0.049). Furthermore, major complications were more common among those undergoing open insertion, whether as a stand-alone or at the time of staging laparoscopy (n = 11/71), as compared with insertion at the time of oesophagectomy (n = 3/86, P = 0.011).
Conclusions
This report represents the largest to our knowledge single-centre comparison of open vs. laparoscopic jejunostomy insertion in patients undergoing oesophagectomy in the treatment of gastroesophageal malignancy. We conclude that the laparoscopic jejunostomy insertion technique described represents a safe and effective approach to enteral access which may offer superior outcomes to conventional open procedures.
Barrett's oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. ...Barrett's oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett's oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett's oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett's oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett's oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice.
PDF
