Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process.

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

Minimally invasive esophagectomy and its current role in esophageal cancer.

The incidence of esophageal cancer has increased over the previous 4 decades. In 2014 alone, it is estimated that there will be 18,000 patients diagnosed with esophageal cancer, and 15,000 deaths from the disease.Esophagectomy, most commonly with adjuvant chemotherapy and radiation to treat locoregional spread, is the primary vehicle to offer patients cure. Open approaches (transthoracic Ivor Lewis, transhiatal, left thoracoabdominal, and 'three phase' McKeown esophagectomy) have been the most common, and are associated with significant morbidity and mortality.With this morbidity in mind, minimally invasive esophagectomy (MIE) has gained enthusiasm from the surgical community as an approach to minimize post-operative morbidity without sacrificing long-term outcomes. In this article, we review the basic steps of the three major approaches to MIE. We also review the recent data which supports the surgical field's growing enthusiasm for this approach to esophageal cancer. Based on our review of current data, we conclude that patients undergoing MIE have improved short-term outcomes with regard to morbidity and quality of life, with no adverse effects of the quality of oncologic resection.

A preliminary experience with minimally invasive Ivor Lewis esophagectomy.

With several small series examining minimally invasive Ivor Lewis esophagectomies, we look to contribute to a growing experience. In reporting our initial results, safety, initial oncologic completeness, and preliminary outcomes with a minimally invasive Ivor Lewis esophagectomy were demonstrated. From 2007 to 2010, 40 minimally invasive Ivor Lewis esophagectomies were carried out. The approach was a laparoscopic mobilization of the stomach and a thoracoscopic esophageal mobilization and creation of a high intrathoracic anastomosis. Indications included esophageal cancer in 39 patients and esophageal gastrointestinal stromal tumor in one patient. Median age was 62 (range 39-77) with 31 (78%) male patients. Non-emergent conversion was required in two (5%) patients. Twenty-five (63%) patients underwent neoadjuvant therapy. Mean operative time was 364 minutes (range 285-455), and mean blood loss was 205 cc (range 100-400). All patients underwent an R0 resection including the removal of all Barrett's esophagus, and mean number of nodes harvested was 21 (range 11-41). Median intensive care unit stay was 1 day (range 1-3), and hospital stay was 7 days (range 6-19). There were no anastomotic leaks and no 30-day mortality. Postoperative complications included eight (21%) patients with atrial fibrillation and two (5%) chylothorax, one requiring ligation. At a mean follow-up of 16.5 months (range 1-39 months), five (13%) patients have had a distant recurrence; there have been no local recurrences. Minimally invasive Ivor Lewis esophagectomy, although technically challenging, can be carried out with reasonable operative times, a short length of stay, and minimal complication. Final oncologic validity is pending longer follow-up and a larger series.

Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells.

Fatty acid ethyl esters (FAEE), esterification products of fatty acid and ethanol, have been implicated as mediators of ethanol-induced organ damage. To understand the molecular and cellular events in FAEE synthesis and secretion, we developed a system in which HepG2 cells synthesize and release FAEE into the culture medium upon incubation with ethanol. The synthesis of FAEE was observed within 5 min of the addition of ethanol, with a plateau for FAEE synthesis after 2 h of incubation. It was also observed that FAEE are synthesized by both a microsomal FAEE synthase, which preferentially uses fatty acyl-CoA as a substrate, and a cytosolic FAEE synthase, which accepts both unesterified fatty acid and fatty acyl-CoA as substrates with a slight preference for fatty acyl-CoA. Although the kinetics of cellular FAEE synthesis await further characterization, the intracellular fatty acid substrate appears to be derived principally from glycerolipids and other esters. FAEE were released into the culture medium by a mechanism independent of the vesicular transport pathway. Lipoprotein particles and albumin were found to be carriers of FAEE after FAEE secretion from the cell.

Fatty acid ethyl esters in the blood as markers for ethanol intake.

OBJECTIVE: To determine the clinical utility of fatty acid ethyl esters (FAEEs) in the blood as a short-term confirmatory marker for ethanol intake and a longer-term marker for ethanol intake after ethanol is no longer detectable. DESIGN: Single-center controlled clinical trial and a blinded comparison involving 48 blood samples that were positive, negative, or equivocal for blood ethanol. PARTICIPANTS: Seven healthy subjects (4 men and 3 women, aged 21 to 23 years) participated in the clinical trial. Blood samples from participants for the blinded comparison portion of the study were numbered from 1 to 48 and not identified by name. INTERVENTION: The 7 healthy subjects ingested a known amount of ethanol at a fixed rate. The concentration of FAEEs in the blood after ethanol intake was determined for a period of up to 24 hours. There was no intervention in the blinded comparison study. MAIN OUTCOME MEASURES: In the clinical trial, a pharmacokinetic analysis of FAEE concentration in the blood after ethanol intake was completed for 7 individuals whose blood ethanol level was elevated from 25 to 35 mmol/L. In the blinded comparison, the 48 blood samples that were positive, negative, or equivocal for blood ethanol were analyzed for FAEE concentration. RESULTS: In the clinical trial, the disappearance of FAEEs from the blood followed a decay curve that initially resembled the decay curve for blood ethanol. However, because of a very slow secondary elimination phase, the FAEEs were found to persist in the blood for at least 24 hours after ethanol intake was completed. In the blinded comparison, all 20 samples that were positive for ethanol were positive for FAEEs, 7 of 7 samples equivocal for ethanol were positive for FAEEs, and 21 of 21 negative samples for ethanol were negative for FAEEs. CONCLUSIONS: Serum concentration of FAEEs can serve as an excellent short-term confirmatory test for ethanol intake as well as a longer-term marker of ethanol ingestion. Measurement of FAEEs in the blood may be a more sensitive indicator of ethanol ingestion than the measurement of blood ethanol .

Fatty acid ethyl ester synthase catalyzes the esterification of ethanol to cocaine.

Fatty acid ethyl esters (FAEE), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs damaged by ethanol abuse. Cocaethylene is a cocaine metabolite generated in the presence of ethanol which has been established as enhancing cocaine toxicity. In the present study we show that purified FAEE synthase also catalyzes the formation of cocaethylene. A linear relationship (r = 0.998) was demonstrated between the amount of purified FAEE synthase (microgram) and cocaethylene synthesis (nmol/hr). We further showed a correlation (r = 0.804) between the two enzyme activities in selected tissues. These findings provide evidence that purified FAEE synthase has cocaethylene synthetic ability and FAEE synthase may be responsible for a portion of cocaethylene synthesis in vivo.