Fast-track surgery after gynaecological oncological surgery: A Prospective Randomized Trial

Background: Fast-track surgery (FTS)or enhanced recovery after surgery have been applied to many surgical procedures. The FTS interventions may lead to a major reduction in the undesirable sequelae of surgical injury with improved recovery and reduction in postoperative morbidity and overall costs. The aim of this study is whether FTS reduces the length of stay in hospital compared to traditional management. The secondary aim is whether FTS is associated with an increase in post-surgical complications compared to traditional management (for both open and laparoscopic surgery). Methods: A prospective randomized trial included 107 patients undergoing gynaecological oncological surgery. The patients were randomized to the FTS group (n=50) and the traditional group (n=57). LOS (Length of stay in hospital), and complications were assessed. Results: No signi ﬁ cant differences in LOS were observed between the groups. The total costs of hospitalization (RMB), and CRP (C-Reactive protein mg/l) are less in the FTS group (P < 0.05) and the overall complications were lower in the FTS Group, statistically signicantly lower ((P < 0.05). Conclusions: Fast-track surgery after gynaecological oncological surgery is benecial for patients.


Background
Fast-track surgery (FTS) or enhanced recovery after surgery (ERAS) have been applied to many surgical procedures. The FTS interventions may lead to a major reduction in the undesirable sequelae of surgical injury with improved recovery and reduction in postoperative morbidity and overall costs (1).Surgical injuries in the organ are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biological cascade systems (cytokines, complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc) (2). Although FTS has been adopted in gynaecological, colorectal and upper GI specialties worldwide, and has been used successfully in pancreatic surgery, but initial studies in gynaecology surgery only included hysterectomies for benign indications or precancerous lesions. (3) A recent surgical study suggested that FTS was as safe as conventional perioperative care and improved recovery of patients undergoing pancreaticoduodenectomy, thus reducing in-hospital costs. The general adoption of FTS protocols during pancreaticoduodenectomy should be recommended. (4) As well as FTS program is safe, feasible, and can be applied successfully in liver resection. (5) It is well known that surgical stress induces a catabolic state that leads to increased cardiac demand, relative tissue hypoxia, increased insulin resistance, impaired coagulation pro les, and altered pulmonary and gastrointestinal function. FTS were developed with the goal of maintaining normal physiology in the perioperative period, thus optimizing patient outcomes without increasing postoperative complications or readmissions.(6) FTS have been developed in gynecologic surgery since 2006.(7)And guidelines from ERAS have been published and recently updated.(8) FTS programs have been developed globally to decrease perioperative stress, improving pain management and gut dysfunction, and minimizing postoperative complications which will then lead to hastened patient recovery and reduced time in hospital. (9) On average, more than 400 gynaecological oncological surgeries were performed in our hospital every year, and no FTS was carried out before 2016, therefore we registered a protocol in clinical trials, trial registration number: NCT02687412. Approval Number: SCCHEC20160001 on 23 February 2016. We did this randomized controlled clinical trial (RCT) during 2017-2018. We nished the RCT and analysed all the data before 23th April 2018, and we release it on clinical trial on 25th August 2019.  . Patients with primary nephrotic or hepatic disease 7. Patients with severe hypertension de ned as systolic blood pressure ≥ 160 mmHg and diastolic blood pressure > 90 mmHg.

Materials And Methods
Criteria for discontinuing 1) the trial appears causing unexpected harm or severe adverse events to participants, or the evidence that the risks outweigh the bene ts, with the discontinuance decision of the ethics committees.
2) the enrollment indicates the trial can't be nished in a period of 3 months.

Fast track and traditional management
See Discharge criteria were stability of vital signs, alert and oriented state of consciousness, absence of complications or symptoms, autonomous walking, possibility of feeding with a solid diet, successful rst atus, spontaneous diuresis, good control of pain numeric rating scale (NRS) < 4 with oral medications, self-su ciency in basic daily activities and the desire expressed by the patient to go home.

Randomization
Women who met the eligibility and completed a baseline visit were randomized into one of the two groups at a ratio of 1:1. Women were allowed to complete the baseline and randomization visit on the same day. The allocation sequences were generated by investigators utilizing computer-generated random number. To reduce predictability of a random sequence, details of any planned restriction (e.g. blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions.
Data will be analyzed using SPSS 18.0 (IBM Corp., Armonk, NY, USA) and expressed as mean ± SD. LOS, postoperative hemorrhage, post-operative thrombosis in the FTS and traditional groups will be compared and analyzed using the Student's t-test. The chi-square test or Fisher's exact test will be used to analyze the categorical secondary endpoints (complications). P < 0.05 will be considered statistically signi cant. (min) while the traditional group was 200.37(min). The estimated blood loss during surgery of the FTS group was 320.00 and the traditional group was 280.18. The patient data in the two groups are summarized in Table 5. 6. Patients with primary nephrotic or hepatic disease 7. Patients with severe hypertension de ned as systolic blood pressure ≥ 160 mmHg and diastolic blood pressure > 90 mmHg. Table 3 Criteria for discontinuing 1. the trial appears causing unexpected harm or severe adverse events to participants, or the evidence that the risks outweigh the bene ts, with the discontinuance decision of the ethics committees.

Results
2). the enrollment indicates the trial can't be nished in the period of 3 months.   (Table 6).  The cost of surgical therapy (RMB) and Calcitonin original PCT were (9703.22 versus9538.47 and 0.5595 versus 0.5212 respectively) but these differences had no statistical significance. Table 8. Statistical analysis including descriptive statistics, and the chi-squared test for complication.
The overall complications (3 in the FTS group, 13 in the traditional group) were not signi cantly different statistically (sig 0.014) ( Table 9). While the complication of infections in the FTS group was found to be less compared to the traditional group (sig 0.034). Table 9.  There are some studies demonstrate that FTS implementation in gynaecologic oncological surgery is associated with LOS decrease without increases of morbidity or readmission rates. (10,11).But in this prospective randomized clinical trial, it appears that the LOS is nearly the same between two groups. The reasons seem are as follows. First compared with general surgical oncology surgery, gynecological oncological surgery leads to less damage, almost has done no serious damage to the digestive tract. Second, compared with general surgical oncology surgery, gynecological oncological surgery hardly has a serious complication such as digestive tract stula or leakage and death. Third, we did not include older patients (age ≥ 71 years) after discussion with the ethics committee, considering the slow recovery of digestive system and more basic diseases. Finally, part of patients continued to receive chemotherapy after surgery, and we do not discharge on the weekend or holidays, this made the criteria for discharge unstable.
We are happy to see the total cost of hospitalization (RMB) was significantly lower in the FTS group compared with the traditional group. One of the important procedures we conducted was using a heating blanket to avoid hypothermia, keeping the intra-operative core-temperature at 36 ±0.5℃. Unintentional hypothermia is de ned as an accidental low body temperature. (12) The National Institute for Health and Care Excellence (NICE) estimates that 70% of patients admitted to the anesthetic recovery room suffer from hypothermia. (13)The accidental perioperative hypothermia is a common event during surgical interventions and increases itself perioperative morbidity impairing hemostasis, wound healing, and increasing cardiac events. (14) Because intraoperative body temperature maintenance signi cantly shortened the postoperative anesthesia resuscitation time, the application time of ventilator was reduced and the cost was signi cantly reduced. Meanwhile, fast-track surgery reduced the overall complications and complications of infections and was found statistically signi cant, while there was no statistical difference in some other complications. Therefore, the cost of treatment was lower than that of the traditional group.
The early oral feeding and shorter duration of intravenous infusion, reduce the costs for parenteral nutrition and prevention of thrombosis and so on. The CRP (C-Reactive protein mg/l) was also significantly lower in the FTS group compared with the traditional group. Fasting from midnight increases insulin resistance, a complex clear carbohydrate-rich drink designed for use within 2h before anesthesia reduced hunger, thirst, anxiety as well as postoperative insulin resistance. (15)  Early postoperative diet speeded up gastrointestinal motility, so we found days of fasting is much shorter in the FTS group.
In this prospective randomized trial, the cost of surgical therapy (RMB) is nearly the same between the two groups. And there was no signi cant difference in the cost of surgical therapy (RMB) as the two groups had the same operators.
The incidence of total postoperative complications and lower infection rates were considered to be closely related to preoperative anxiety reduction, intraoperative temperature control, and postoperative glycaemic control. FTS program shortens preoperative and postoperative fasting time and decreases the amount of time patients staying in bed. This can be detrimental to recovery as it can result in a negative nitrogen balance. (17) The FTS program's early oral feeding protocol assists in optimal wound healing.
Research shows that unrelieved pain can inhibit the immune system, decrease gastrointestinal motility and lead to respiratory dysfunction by increasing oxygen demand.(18) As early mobility is an essential component of the FTS program, analgesia must allow mobilization and participation in recovery by the patient. Patients of ovarian cancer after appendectomy would fast until anal exhaust in the traditional sense, but early feeding proved safe and effective in the recent consensus guidelines for enhanced recovery after gastrectomy and pancreaticoduodenectomy. (19,20) It is also safe for ovarian cancer patients.
In summary, gynecological oncological surgeries have little damages to the digestive tract, so fast track surgery is appropriate and safe for them. This approach not only decreases the complications of infection also decreases the total cost of hospitalization. The ultimate bene ts of FTS are improving outcomes, decreasing total cost and faster recovery.

Compliance with Ethical Standards
Disclosure of potential con icts of interest There is no potential con icts of interest.

Research involving human participants
Informed consent: All participants signed informed consent.
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of an independent ethics committee at Sichuan Cancer Hospital and Research Institute. Board A liation: SichuanCHRI. After Ethics approval was granted, the FTS Database was searched to identify patients operated upon between May 2016 and May 2018.