The Safety and Efficacy of Enhanced Recovery After Surgery on Clinical and Immune Outcomes for Gynecological Oncology

Study Overview
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Brief Summary
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The aim of this study is to compare outcomes of enhanced recovery after surgery (ERAS) procedure, involving preoperative, intraoperative and postoperative optimization, with those of conventional treatment procedure in women undergoing laparoscopic surgery for gynecologic cancer or suspected gynecologic cancer. Investigators hypothesize that those patients randomized to the ERAS protocol will have better recovery status, shorter lengths of hospital stay, without increasing readmission rates and complications, compared with traditional treatment.

Detailed Description
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Over the past two decades, enhanced recovery after surgery (ERAS) has been initiated and developed in colorectal surgery by Kehlet. Studies have demonstrated that ERAS program can reduce length of hospital stay, hospital cost, complications and morbidity and improve the quality of patient recovery in colorectal, urologic, thoracic, orthopedic, and vascular surgeries by randomized trials and meta-analyses. However, the data in gynecologic oncology underwent minimally invasive therapy is scarce. Therefore, the aim of this study is compare outcomes of ERAS procedure with conventional treatment procedure, to provide practical experience and guidance for the treatment of gynecologic cancer in the future. The study is a single-center randomized control trial (RCT), and 80 cases of gynecological malignancy in Shanghai First Maternity and Infant Hospital from 2018 to 2021 will be enrolled in this research. All patients with a known or suspected gynecologic malignancy scheduled for laparoscopic surgery will be screened for study eligibility. Those eligible for the study will be approached for participation in the study and provided written informed consent. The randomization sequence of group allocation by means of computer-generated random numbers was generated by an independent statistician from Tongji University. For ERAS group, patients would receive an optimized preoperative, intraoperative and postoperative care, including extensive preoperative counselling, no mechanical bowel preparation, nonselective NSAIDs premedication, no preoperative fasting but with preoperative carbohydrate loading, tailored anaesthesiology, non-opioid pain management, early removal of urinary catheter, early postoperative feeding and mobilization, and postoperative antiemetic and analgesia management. For control group, patients would receive standard conventional procedure. After meeting the discharge criteria, patients would discharge and additionally follow-up in gynecologic oncology clinic at 2 weeks and 6 weeks postoperatively. Primary outcome measure of the study involves operation length(h), intraoperative blood loss(mL), intraoperative fluid transfusion units(mL), intraoperative urinary volume(mL), intraoperative blood transfusion(mL), postoperative vital signs, Visual Analog Score (VAS) scale, Post Operative Nausea And Vomiting (PONV) status, first exhaust defecation time, ambulation, length of stay, hospitalization expense, albumin and prealbumin, and postoperative complications. Apart from clinical outcomes, the immunological indicators will also be assessed, consist of WBC, neutrophil count (NEUT), C-Reactive Protein (CRP), CD3+ T cells, CD4+ T cells, CD8+ T cells, CD4+/CD8+ T cells preoperatively, and on post-operative day 1(POD1), POD3, POD5. In addition, the anxiety and sleep quality indicators were analyzed by questionnaire preoperatively and POD5. For statistical analyses, categorical variables were described using counts and frequencies, and quantitative variables were described using mean, medians and ranges. Patients' characteristics and distribution were compared with MannWhitney U and χ2 tests. The level of statistical significance was set at P< 0.05. Statistical analyses were carried out with the SPSS 20.0.

Official Title
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Shanghai First Maternity and Infant Hospital

Conditions
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Gynecologic Cancer

Intervention / Treatment
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* Procedure: ERAS procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly pathological diagnosed and suspected gynecologic tumors, including cervical cancer, ovarian cancer, endometrial cancer, fallopian tube cancer, uterine carcinosarcoma, and choriocarcinoma. Ages range from 18 to 70. body mass index of between 18 and 35. American Society of Anesthesiologists (ASA) grading of I to III. No history of abdominal surgery and severe organ dysfunction such as heart and lung. Exclusion Criteria: Unwillingness to participate. Inability to give written informed consent. Absolute contraindication for surgery. History of other malignancies, radiotherapy and chemotherapy. Uncontrollable Cardiovascular and cerebrovascular diseases, diabetes, and liver and kidney dysfunction.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ERAS procedure<br>In this arm, ERAS perioperative cares patients planned to undergoing laparoscopic surgery, following the ERAS protocols. Extensive preoperative counselling and education by surgeon and anesthetists. No Bowel preparation. 6 h fast for solid food and carbohydrate loading with clear fuilds 2h before surgery. Oral nonselective NSAIDs premedication. Total Intravenous Anesthesia via TCI, wound infiltration and the transversus abdominis plane (TAP). Minimally invasive surgery. Maintenance of normothermia. Avoidance of surgical drains and nasogastric tubes. Nonselective NSAIDs postoperative medication. Postoperative nausea and vomiting active control. Early oral feeding and ambulation. VTE prophylaxis postoperative. | Procedure: ERAS procedure<br>* Optimized preoperative, intraoperative and postoperative procedures.<br>|
| No Intervention: Traditional treatment procedure<br>In this arm, control patients planned to undergoing laparoscopic surgery, following the traditional treatment protocols. Conventional preoperative visits and education. Mechanical bowel preparation. Fasting overnight, and no fluids before surgery. No oral nonselective NSAIDs premedication. Continuous epidural anesthesia is administered before surgery. Sevoflurane and sufentanil maintain the depth of anesthesia. Minimally invasive surgery. No maintenance of normothermia. Drainage tube insertion if needed. Postoperative patient-controlled intravenous analgesia. Postoperative Nausea Control if needed. Conventional oral feeding and mobilization. No bowel routine. VTE prophylaxis postoperative. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total length of hospital stay (days) | Total length of hospital stay (days) | Up to 20 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operation Time(h) | Operation Time(h) | The day of surgery | 
| Intraoperative blood loss(mL) | Blood loss during the operation | The day of surgery | 
| Intraoperative fluid transfusion units(mL) | Fluid transfusion units during the operation | The day of surgery | 
| Intraoperative urinary volume(mL) | Urinary volume during the operation | The day of surgery | 
| Intraoperative blood transfusion(mL) | Urinary volume during the operation | The day of surgery | 
| Visual Analog Score (VAS) for pain | Visual Analog Score (VAS) for pain | Up to 5 days after surgery | 
| Post Operative Nausea And Vomiting (PONV) status | Post Operative Nausea And Vomiting (PONV) status | Up to 5 days after surgery | 
| Time of off-bed activity per day | Postoperative activity | 1 week | 
| Distance of off-bed activity per day | Postoperative activity | 1 week | 
| First exhaust defecation time | Bowel function recovery | Up to 3 days after surgery | 
| Albumin | Nutritional indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| Prealbumin | Nutritional indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| WBC | Immunological indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| Neutrophil count (NEUT) | Immunological indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| C-Reactive Protein (CRP) | Immunological indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| CD4+ | Immunological indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| CD8+ | Immunological indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| CD4+ / CD8+ | Immunological indicators | Before the operation, on Postoperative Day 1, Postoperative Day 3 and Postoperative Day 5 | 
| Hospitalization Expense | Medical expense | Up to 1 month after surgery | 
| Anxiety indicators | Anxiety index were tested by questionnaire of self-rating anxiety scale(SAS) on preoperation and Postoperative Day 5 | Before the operation and Postoperative Day 5 | 
| Sleep quality indicators | Sleep quality index were tested by questionnaire of Pittsburgh sleep quality index(PSQI) on preoperation and Postoperative Day 5 | Before the operation and Postoperative Day 5 | 
| Postoperative complications | Postoperative complications | Up to 1 month after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gynecologic Cancer, Enhanced Recovery After Surgery, Laparoscopic surgery