Feasibility and Effectiveness of Three-day Discharge After Distal Pancreatectomy

1\. BACKGROUND AND RATIONALE Over the years, improvements in the management of patients undergoing pancreatic surgery have contributed to enhancing postoperative outcomes and patient recovery. This progress is largely attributed to the centralization of care in high-volume centers. The integration of minimally invasive techniques (such as laparoscopic and robotic surgery), and the adoption of Enhanced Recovery After Surgery (ERAS) protocols. Despite these advancements, the average length of stay (LOS) after distal pancreatectomy (DP) remains around 5 to 7 days. Extended hospital stays often arise from postoperative complications, which occur in approximately 40% of cases following DP. Among these complications, clinically relevant pancreatic fistula (CR-POPF) is the most frequent, affecting up to one-third of patients. However, in most cases, POPF following DP is managed conservatively by simply maintaining the abdominal drain placed intraoperatively. POPF can eventually lead to intra-abdominal fluid collections but rarely to more severe complications such as delayed gastric emptying (DGE), and post-pancrectomy hemorrhage (PPH). Delays in hospital discharge often occur in patients who have already achieved functional recovery, but stay in the hospital due to nonclinical factors such as healthcare system culture or concerns from both surgeons and patients about early discharge.

An early discharge program in selected patients has been successfully demonstrated in colorectal and bariatric surgery. Studies indicate that performing these procedures in an outpatient setting is both feasible and safe, provided upon careful patient selection, patient education, strict adherence to ERAS protocols, and effective follow-up via phone or app-based systems. The advantages of outpatient surgery have been shown to reduce healthcare costs and decrease the wait times for surgery while maintaining equivalent care quality and readmission risk. Although outpatient surgery would be unrealistic for pancreatic surgery, an early discharge program (i.e., before POD5) to patients undergoing DP could yield similar benefits as observed after colorectal surgery. However, the feasibility of an early discharge program has yet to be evaluated in this specific population. The hypothesis is that an early discharge protocol could be effective and feasible in patients undergoing minimally invasive DP, within a preoperative educational program and an adequate telephone follow-up after discharge, without increasing access to ED visits or hospital readmission.

Previous experience and ongoing studies The Division of Pancreatic Surgery at San Raffaele Hospital is among the leading centers for pancreatic surgery in Italy, performing over 300 pancreatic resections annually for the past five years. A prospective quality-improvement registry has been maintained since 2015, encompassing perioperative data from over 2000 patients. In 2023 alone, our division conducted 340 pancreatic resections, including 205 pancreatoduodenectomies, 106 distal pancreatectomies, and 23 total pancreatectomies.

For DP, a minimally invasive approach is preferred for patients with benign or selected malignant lesions, based on factors such as lesion location, vascular involvement, and extent of parenchymal resection required. In our experience, approximately two-thirds of DPs are performed laparoscopically, with a conversion rate to open surgery lower than 10%. Postoperative discharge typically occurs around 7 days after surgery (IQR 6-10), with functional recovery achieved by day 5 (IQR 4-6). Discharge criteria include the ability to tolerate solid food, independence from intravenous fluids, restored gastrointestinal function, sufficient pain management with oral analgesics, independent mobilization, the absence of clinical complications, and the patient's willingness to leave the hospital. In our previous experience, 30% of patients achieved discharge criteria within three days after surgery and underwent an early discharge without 30-day emergency department (ED) visits or hospital readmission, underling the safety of an early discharge protocol. Similar results were found in a different study by the University Hospital Southampton researchers, where they have shown that implementation of ERP (enhanced recovery programme) optimizes outcomes for laparoscopic distal pancreatectomy, with significant earlier return to normal gut function and reduced length of stay, with a median length of stay of 3 days after surgery, without increasing the readmission rate.

For patients with pancreatic fistula, discharge often involves an abdominal drain, with follow-up outpatient visits on POD 7 and POD 15.

Our previous studies show that 19% of patients undergoing laparoscopic DP require emergency department visits (ED) after discharge, and 76% of these patients are readmitted to the hospital, primarily due to intra-abdominal collections. Currently, around 25% of patients are discharged with an abdominal drain due to the presence of an amylase-rich fluid in the abdominal drain. However, previous studies have shown that keeping the drain in place for elevated postoperative amylase levels does not significantly protect against intra-abdominal collections, which may still require antibiotics or operative management. Additionally, the median time for hospital readmission is three weeks after surgery and most postoperative CT scans that reveal complications are performed beyond 10 days after surgery, suggesting that a short hospital stay would not impact readmission rates or necessitate additional interventions. Considering these factors and the PANDORINA trial which underlines the feasibility and safety of a no-drain policy after DP with a reduction in CR-POPF and length of stay, a no-drain approach for patients undergoing minimally invasive DP is adopted. In cases of intraoperative complications or when deemed necessary by the surgeon, an abdominal drain is placed with amylase levels measured on POD1 and POD3. Drains are removed on POD1 if amylase levels are \<2000 U/L.

Research Objective:

The objective of this study is to investigate the feasibility and effectiveness of a 3-day discharge protocol following a minimally invasive distal pancreatectomy, with post-discharge phone follow-up conducted by a nurse navigator, which is a nurse uniquely qualified to provide phone support to patients and caregivers throughout the care trajectory and to collect information about clinical health conditions of patients after surgery,

Research Hypothesis:

Our observational prospective cohort study is designed to address several key research questions:

* Can patients undergoing minimally invasive distal pancreatectomy be feasibly discharged on POD3? * Is POD3 discharge effective for patients following minimally invasive distal pancreatectomy? * What is the rate of 30-day emergency department visits and hospital readmissions associated with an early discharge protocol? * What are the primary reasons for emergency department visits, and which of these are potentially preventable? * How satisfied are patients with the early discharge protocol?

OBJECTIVES AND ENDPOINTS Primary Objective: To investigate the feasibility of a 3-day discharge protocol following a minimally invasive distal pancreatectomy, with post-discharge phone follow-up conducted by a nurse navigator.

Secondary Objective: To investigate the effectiveness of a 3-day discharge protocol following a minimally invasive distal pancreatectomy, evaluate the rate of 30-day emergency departement visits, hospital readmission and patient satisfaction Primary Outcome The feasibility of the 3DD protocol, will be defined as successful discharge on Post Operative Day (POD)3 without any Emergency Department (ED) visits within POD7. The benchmark for feasibility will be considered at 75% Secondary Outcome Effectiveness defined as no development of severe complications (Clavien Dindo Classification ≥ 3) within 7 POD.

STUDY DESIGN This is an observational prospective cohort study that will be conducted at San Raffaele Hospital (Milan, Italy) and was developed according to STROBE guidelines

Study duration Duration of enrollment: 12 months Duration of total follow-up: 6 months Duration of total study period: 18 months

In the Division of Pancreatic Surgery, approximately 110 patients undergo DP each year and 70 are performed laparoscopically. Considering a similar 43% preoperative exclusion rate and a potential 23% dropout rate post-enrollment reported in previous colorectal population, the estimated recruitment period to achieve the target sample size of 30 patients is approximately 12 months. With an additional 6 months required to finalize patient follow-up, data analyses, and manuscript preparation. The time required to complete this study is approximately 18 months.

STUDY POPULATION All patients undergoing elective minimally invasive distal pancreatectomy who meet the following inclusion criteria will be included in this study.

Inclusion Criteria

* adult (age≥ 18 years) patients undergoing elective minimally invasive distal pancreatectomy * patients residing or with a temporary accommodation within 50 km or a 30-minute drive from the hospital; * patients with an adequate support system at home (defined as 24-hour support for at least the first POD7); * no contraindications to intrathecal or opioid-sparing analgesia; * patients who have signed the informed consent for participation in the trial; * no preoperative medical issue requiring inhospital observation longer than three days Exclusion Criteria * Patients undergoing multi-visceral resection; * undergoing an open procedure; * requiring vascular resection; * having a history of chronic opioid use; * having significant comorbidities or an American Society of Anesthesiologists (ASA) score \> 3; * patients unable to speak Italian; * having a cognitive impairment; * developing intraoperative complications; difficulty to be reached after discharge (e.g., limited access to a telephone).

STUDY OBJECT This study aims to evaluate the feasibility and safety of a three-day discharge (3DD) protocol for patients undergoing minimally invasive DP. All procedures, clinical evaluations and follow-up will correspond to current clinical practice.

Study object description Preoperative counseling During preoperative counseling with a surgical resident, all patients will receive information about the surgical procedure, expected postoperative care, and scheduled follow-up after discharge, both verbally and through informational booklets Intraoperative anesthesia and procedure The anesthetic regimen will adhere to institutional guidelines (see Appendix 2). Prior to the surgical procedure, all patients will receive intrathecal analgesia with morphine administered at the T7-9 level (0.15-0.2 ml). General anesthesia will be induced with fentanyl (1-2 mcg/kg), propofol (2 mg/kg), and either rocuronium (0.6 mg/kg) or cisatracurium (0.5 mg/kg), with maintenance provided by inhaled anesthetics.

Surgical procedure: all patients will undergo elective minimally invasive distal pancreatectomy with or without splenectomy. A Pfannenstiel incision will be used for specimen extraction. In patients deemed at high risk of pancreatic fistula according to validated risk scores (e.g., Distal Fistula Risk Score) or experiencing intraoperative complications, the placement of an abdominal drain at the end of the surgical procedure will be considered. In all other patients, no abdominal drain will be placed.

In-hospital postoperative care Postoperative analgesia will be managed with acetaminophen administered three times a day around the clock, along with NSAIDs as needed, starting at the end of surgery. On POD 1, oral tapentadol will be initiated at a starting dose of 50 mg every 12 hours, with this therapy discontinued after POD 7. A detailed ERAS protocol can be found in Appendix 2.

On POD 0, all

• Percentage of patients with no development of severe complications within 7 POD [Срок оценки: 7 days post surgery and 30 days post surgery]