ERGS Study

Responsabile: Dott. U. Fumagalli Romario

Enhanced Recovery in Gastric Surgery

(ERGS-study)

Date: January 29, 2015

1. ABSTRACT: 

Objective: In the last few years the concept of a ‘enhanced recovery after surgery’ (ERAS) has been developed and applied, mainly in the field of colorectal surgery, where it has revolutionized the perioperative care for these patients and is now applied in routine clinical care. Optimal pain management, early enteral nutrition and aggressive mobilization are the mainstay of the ERAS philosophy. The application of ERAS programs in gastric surgery has been more difficult, partly because it included some radical changes in comparison to daily practice in this field of surgery, such as perioperative nutritional programs. Some recent studies have demonstrated that ERAS protocols can be successfully applied to gastric resective surgery

Aim of study: the aim of this study is to evaluate the applicability of a standardized ERAS protocol to patients undergoing gastric resective surgery.

Methods: a multi-centre prospective observational phase II study will be conducted on patients scheduled for gastric resective surgery. 

A standardized perioperative pathway will include, preoperatively, an evaluation and optimization of risk factors, identification of nutritional problems with administration of immunonutrition, patient counseling and explication of the clinical pathway. Intra and post- operative management will be based, among others, on a fluid restriction policy, use of nutritional facilities, early enteral feeding and mobilization, optimal pain management.

Primary endpoint will be the number of patients with full or partial adherence to ERAS protocol. Secondary endpoints will comprehend overall morbidity rate (any diagnosed morbidity within 30 days from surgery); number of patients reaching full postoperative discharge criteria on POD 5; length of postoperative stay; readmission rate; number of protocol violation and reason for protocol violation.

1. PROPOSAL
2. Title of the study: 

Enhanced Recovery in Gastric Surgery  (ERGS-study)

1. Principal  Applicants:

Uberto Fumagalli Romario, Upper Gastrointestinal Surgery, Humanitas Research Hospital, Rozzano, Italy (uberto.fumagalli@humanitas.it).

Luca Gianotti, Associate Professor of Surgery – University of Milano-Bicocca – General  Surgery – Ospedale di San Gerardo, Monza, Italy – (luca.gianotti@unimib.it)

Will be in charge of coordinating the study.  They will be responsible for the clinical aspects of the study in their center and will be responsible of data collection at their center. They will be responsible of collecting the data from the other centers. After receiving the data from the other centers involved in the study, they will be responsible for data evaluation.  They will be responsible of data publication together with the other co-applicants, basing on the number of included patients.

1. Co-applicants:

We plan to include other Italian Centers in the following months, in order to have at least 5 centers recruiting patients

They will be responsible for the clinical aspects of the study in their center and will be responsible of data collection at their center. They will cooperate with other applicants in evaluating and publishing the data.

Monitoring:  three experts in gastric surgery will be designed as member of ERGS Trial Monitoring Committee. They will have access to the data during the whole course of the study and indicate cessation of the trial if safety concerns, deriving form protocol application,  should be raised during the study.

1. Duration of the project

We hypothesize to include 200 patients in the study and a center recruitment of 10 patients a year. We hypothesize to be able to start recruitment for this study on February 2015; we will recruit patients until reaching the study number of patients. We plan to close recruitment in 2 years.  All included patients will be followed up (after discharge) at one month after surgery.  The study is supposed to close in March 2017. Three months will be necessary for data evaluation, from April 2017 until June 2017.

1. Hypothesis/Aim

The primary aim will be to evaluate which items of our standardized ERAS protocol are more frequently implemented and the rate of applicability by center. The differences by center will be used to analyze the most important items for achieving better results. We hypothesize that the highest adherence to protocol will imply the greatest benefit of patient recovery.

As secondary aims we want to confirm that a standardized ERAS protocol can be safely applied to patients undergoing gastrectomy, leading to a low rate of postoperative morbidity and a short duration of hospital stay without increasing the re-admission rate. Morbidity, longer hospital stay and readmission rate will be compared center by center and related to the adherence to ERAS protocol.

Definition of overall morbidity rate (any diagnosed morbidity within 30 days from surgery)

Morbidity will be defined as the occurrence of any complication, directly or indirectly related to surgery. Complications will be classified according to Dindo and Clavien [Dindo D., Demartines N., Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13)].

Description of the number of patients reaching full postoperative discharge criteria on POD 5

the discharge criteria will be checked every day from POD 5:

Discharge criteria are:

1. the patient must have achieved full mobilization;
2. pain should be controlled by oral therapy
3. home nutritional requirements are achievable: the patient should have and tolerate enteral feeding and/or oral nutrition with patient able to reach a nutritional intake of at least 60% of daily energy requirement.

Description of the real length of postoperative stay and the reasons for the difference between the reach of discharge criteria and effective postoperative stay will be explained 

Description of the readmission rate:

after discharge patients will be seen at the outpatient clinic at POD 30. Missing patients will be contacted by a phone call in order to identify postoperative morbidity and rehospitalisation rate

1. Background information

The ERAS program has been defined recently has the goal standard of perioperative care of patients undergoing colorectal resection. Up to now there is no unanimous consensus on how many and which one of the classic 18 items are the key ones for a improved outcome.

Recent data suggest that also for major upper GI tract surgery, ERAS can be applied safely and with promising results on primary outcome measures. Nevertheless, the experience is still limited and restricted to far-east countries such as Corea and Japan. No European or Italian data are available.

ERAS program has been developed by combining several evidence-based techniques for perioperative care intended to reduce the stress response and organ dysfunction, and therefore shortening the time required for full recovery and reducing the appearance of serious postoperative complications which are associated with an excessive response to surgical stress.  

Both the surgical approach and the type of perioperative care can have a major influence on the morbidity rate after gastrectomy and probably a comprehensive pathway including an ERAS standardized protocol could be effective in improving the results of this type of surgery.

We think that the feasibility and safety of fast-track rehabilitation programs in patients undergoing gastric resective surgery is set, but there are no convincing data on how the rate of implementation of single items may favorably influence the results of surgical treatment of gastric cancers.  This specific question requires further evaluation in a prospective trial.

References

1. Hosono S, Arimoto Y, Ohtani H, Kanamiya Y. Meta-analysis of short-term outcomes after laparoscopy-assisted distal gastrectomy. World J Gastroenterol 2006; 12:7676–7683.

1. Kim MC, Jung GJ, Kim HH. Morbidity and mortality of laparoscopy-assisted gastrectomy with extraperigastric lymph node dissection for gastric cancer. Dig Dis Sci 2007; 52:543–548.

1. Kim YW, Baik YH, Yun YH, Nam BH, Kim DH, Choi IJ et al. Improved quality of life outcomes after laparoscopy-assisted distal gastrectomy for early gastric cancer: results of a prospective randomized clinical trial. Ann Surg 2008; 248: 721–727.

1. Park JM, Jin SH, Lee SR, Kim H, Jung IH, Cho YK et al. Complications with laparoscopically assisted gastrectomy: multivariate analysis of 300 consecutive cases. Surg Endosc 2008; 22: 2133–2139.

1. Kehlet H,Wilmore DW. Evidence-based surgical care and the evolution of fast-track surgery. Ann Surg 2008; 248:189–198.

1. Kehlet H. Fast-track colorectal surgery. Lancet 2008; 371: 791–793.

1. Petrowsky H, Demartines N, Rousson V, Clavien PA. Evidence-based value of prophylactic drainage in gastrointestinal surgery: a systematic review and meta-analyses. Ann Surg 2004; 240: 1074–1084.

1. Park J, Macleod J, Belza P. Ticket to Home. International Society for Quality in Healthcare. Copenhagen, 2008; http://www.isqua.org [1 May 2009].

1. Grantcharov TP, Kehlet H: Laparoscopic gastric surgery in an enhanced recovery programme. Br J Surg 2010; 97: 1547–1551.

1.  Wang D, Kong Y, Zhong B, Zhou X, Zhou Y: Fast-track surgery improves postoperative recovery in patients with gastric cancer: a randomized comparison with conventional postoperative care. J Gastrointest Surg 2010; 14:620–627.

1. Liu XX, Jiang ZW, Wang ZM, Li JS: Multimodal optimization of surgical care shows beneficial outcome in gastrectomy surgery.  JPEN J Parenter Enteral Nutr 2010; 34: 313–321.

1. Yamada T, Hayashi T, Cho H, Yoshikawa T, Taniguchi H, Fukushima R, et al: Usefulness of enhanced recovery after surgery protocol as compared with conventional perioperative care in gastric surgery. Gastric Cancer 2012; 15: 34–41.

1. Chen Hu J, Xin Jiang L, Cai L, Tao Zheng H, Yuan Hu S, Bing Chen H, et al: Preliminary experience of fast-track surgery combined with laparoscopy-assisted radical distal gastrectomy for gastric cancer. J Gastrointest Surg 2012; 16: 1830–1839.

1. Study design

Study type: Multi-centre prospective observational phase II study.  

Study population: Patients older than 18 yrs scheduled for gastric resective surgery for cancer

Exclusion criteria: ASA > 3 and decompensated ASA 3; gastric outlet obstruction unless fed by enteral feeding (nasojejunal tube/jejunostomy); decompensated diabetes (HbA1c > 7%)

Patient recruitment: patients fulfilling the criteria for gastric resective surgery for gastric cancer (total or subtotal gastrectomy) will be proposed to be included in the ERGS study. After consent is given, the patients will be treated according to the protocol.  Patients refusing to provide informed consent will be treated according to institutional routine protocol.

We expect that each center will include 10 patients/year

Perioperative protocol:

Preoperative

• Evaluation and optimization of risk factors (hypertension, diabetes, COPD, smoke, alcohol, asma, anemia)
• Identification of nutritional problems (BMI – weight loss – calculation of nutritional risk screening score (NRS) and appropriate consequences)
• Immunonutrition (Oral Impact 3 packs/day during 5 o 7* preoperative days)

*If NRS >3

• Preadmission counseling and explication of the clinical pathway (drains and catheters, diet and mobilization protocol; duration of hospitalization, convalescence)
• Preoperative carbohydrate drink (i.e. 4 packs of “Nutricia Preop” the evening before surgery and 2 packs 2-3 hours before surgery either orally or by other enteral route) 
• Mechanical and pharmacological DVT prophylaxis and antibiotic prophylaxis as indicated by specific institutional guidelines

Intraoperative

• Avoid central venous line
• Active patient warming
• Gaol directed fluid therapy (around 4/5 mL/kg/hr colloid or cristalloid) or monitoring by Vigileo, or trans-esophageal doppler or “zero balance” strategy
• If NSR >3 consider placement of a nutritional naso-jejunal tube or a jejunostomy; in any case an indication of daily enteral caloric intake should be registered.
• No NGT (except nutritional tube) at the end of operation
• In subtotal gastrectomy consider avoiding drain placement

Postoperative

• Remove urinary catheter as early a possible, within 3 days
• Fluid restriction: around 1-1,5 mL/kg/hr cristalloid with urinary output 20-30 mL/h if normal renal function
• Nutritional protocol:  
• In patients having an enteral tube: start tube feeding protocol with immunonutrition on postop. Day 1. (use Impact enteral until postop day 7 (up to 1500 ml /day).  Start on day 1 20 ml/h, daily increase 20 ml/h if no adverse event)
• Oral nutrition: consider Gastrographin swallow to check the possibility to comply with nutritional goals (remnant stomach emptying).  Register the day of start liquid diet, and the day of start of soft diet
• In any case register the daily enteral caloric intake.
• Mobilization protocol: encourage patient mobilization on bed after anesthesia recovery and out of bed on POD 1; walk twice a day at least 50 mt on POD 2; walk twice a day at least 100 mt on POD 3
• Pain management: use of peridural catheter infusion until postoperative day 3, or the use of subfascial catheter until postoperative day 3. Avoid morphine. Liberal use of Paracetamol. Patient-controlled analgesia (PCA) if available
• Postoperative counselling: instruct patient on LMWH use and on home jejunostomy feeding
• From POD 5 check the presence of discharge criteria (the patient has achieved fully mobilization; pain should be controlled by oral therapy; home nutritional requirements are achievable: enteral feeding and/or oral nutrition with patient able to reach a nutritional intake of at least 60% of daily energy requirement)

1. Impact on clinical practice and healthcare system

The results of the study are expected to influence significantly the current clinical practice,  defining the optimal perioperative care for patients undergoing gastric resective surgery for cancer of the stomach.  We expect that the application and a strict adherence to the standardized ERAS protocol based on medical evidence could  help in lowering the morbidity rate after gastrectomy, with an effect also on economical health costs.  

1. Track record of applicants including experience in the field and any pilot work carried out

The present ERGS project will be the result of a collaboration between Centers members of the Italian Research Group of Cancer of the Stomach (GIRCG) working actively on Upper Gastro-Intestinal surgery.  

1. Project management structure

The coordinating centers will send to all centers involved in the study an Excel® file for data recording. The coordinating center will be informed by e-mail of any patient included in the study. The mail should be sent at the time the patients signs the informed consent form. After this mail, patient will be registered in the Excel file with an inclusion number.  The including center will receive a confirmation mail with the inclusion number of the patient. 

After completing the study observation time (30 days postoperatively), each patient data will be sent to the coordinating center.

An interim analysis and report to the Ethical committee will be possible during the project. Proposed interval for analysis and reporting will be 1 year, if not suggested differently.

Single applicants will be in charge of data collection, and will take part to data analysis.

1. Dissemination plan

Dissemination of research results, training and exploitation will be actively pursued. Results will be disseminated to the scientific community through specialized media, as selected magazines, conferences, fairs, websites and medical society, including clinicians considered final users and patients. Training activities will be carried out based on the dissemination activities, the target of the courses is expected essentially coming from the medical community.

The objective of the Dissemination Plan is to identify and organize the activities to be performed in order to promote the exploitation of the project's results and the widest dissemination of knowledge from the project.

ERGS trial will establish an infrastructure for communications (and therefore dissemination) by building a robust framework in which dialogue and interaction can take place. This applies equally to internal and external communication. These will be used to disseminate information about and solicit input into the ERAS programs applied to respective gastric surgery.

1. Long term sustainability of the work

The program has the potential for long term sustainability. Should a low postoperative morbidity rate be demonstrated, there will be no reason for not applying in every day care the ERAS protocol to patients undergoing gastrectomy.  There will be no significant increase in health care costs. We expect a short postoperative hospital stay with low rate of readmissions that will guarantee a cost saving.

Enhanced Recovery in Gastric Surgery

(ERGS-study)

1. ISTRUZIONI: 

Ogni Centro viene indicato con una lettera progressiva che viene assegnata dal Centro Coordinatore al momento dell’invio della documentazione per il CE.

Ogni Centro tiene traccia dei pazienti visti e arruolati inserendo i dati nel file “Elenco visti e elenco arruolati”.

Quando un paziente viene incluso nello studio (firma del consenso) deve essere inviata ai centri coordinatori (uberto.fumagalli@humanitas.it e/o   luca.gianotti@unimib.it) una segnalazione che riporti la data di inclusione e le iniziali del paziente. 

Il Centro inviante riceverà una mail di conferma dell’avvenuta segnalazione ed il paziente verrà indicato con in numero composto dalla lettera che indica il Centro e da 3 cifre con il numero progressivo del paziente per il Centro (es.  A001 per il paziente 1 del centro A).

Ogni Centro raccoglierà poi i dati del paziente nel file  di Excel®  “db-eras vers 15-5-15”

I dati inclusi in questo file verranno inviati periodicamente ai Centri Coordinatori

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