Feasibility of a 4-Week Intensive Postoperative Multimodal Rehabilitation Program in Complicated Patients After Proximal Pancreatectomy: A Prospective Single-Cohort Study

Overview

The REACT study is a prospective, single-center, single-cohort study designed to evaluate the feasibility of a 4-week intensive multimodal postoperative rehabilitation program in patients who develop severe complications after proximal pancreatic resection (pancreatoduodenectomy or total pancreatectomy). Postoperative complications after pancreatic surgery may result in substantial physiological and metabolic stress, leading to loss of muscle mass, malnutrition, reduced functional capacity, and delayed recovery. Although prehabilitation programs have been proposed to improve patients' functional capacity before surgery, evidence regarding structured multimodal rehabilitation after pancreatic surgery is currently lacking. Adult patients undergoing elective proximal pancreatic resection who develop a severe postoperative complication (Comprehensive Complication Index \>21) will be eligible for the study. Participants will undergo a 4-week multimodal rehabilitation program starting after hospital discharge and including individualized exercise training, nutritional therapy, and anxiety-reducing techniques. The program may be delivered either in a supervised hospital-based setting or through a home-based program according to patient preference and availability. The primary objective is to assess the feasibility of the rehabilitation program in terms of recruitment, adherence, completion of outcome assessments, completeness of data, and safety. Secondary objectives include evaluating postoperative functional recovery using PROMIS-29 Physical and Mental Health Summary Scores, the 6-minute walk test, and the Duke Activity Status Index. In patients with malignancy who are candidates for adjuvant treatment, return to intended oncologic treatment will also be evaluated. A total of 40 patients will be enrolled and followed for up to 90 days after surgery.

Pancreatic surgery is associated with a high rate of postoperative morbidity. Postoperative complications may impose substantial physiological and metabolic stress, leading to depletion of functional reserves, loss of muscle mass and energy stores, malnutrition, sarcopenia, and reduced functional capacity. Recovery may be particularly prolonged in patients experiencing severe postoperative complications and in frail patients with limited physiological and metabolic reserves. Although multimodal prehabilitation has been proposed to improve functional capacity before major surgery, evidence supporting the role of structured multimodal rehabilitation in improving recovery after pancreatic resection is currently lacking. REACT is a prospective, single-center, single-cohort, low-interventional clinical study conducted at IRCCS Ospedale San Raffaele, Milan, Italy. The study is designed to evaluate the feasibility of a 4-week intensive multimodal postoperative rehabilitation program in patients who develop severe complications after proximal pancreatic resection. All enrolled participants will receive the multimodal rehabilitation intervention in addition to standard postoperative care; no formal comparator group is included. The study population will include adult patients undergoing elective proximal pancreatic resection, defined as pancreatoduodenectomy or total pancreatectomy, who develop a severe postoperative complication during their hospital stay, defined according to a Comprehensive Complication Index (CCI) \>21. The multimodal rehabilitation program will start during the first week after postoperative hospital discharge and will last 4 weeks. The intervention includes exercise training, nutritional therapy, and anxiety-reducing techniques and will be individualized according to the patient's physical, nutritional, psychological, and clinical condition. Activities will be performed under the supervision of qualified healthcare professionals, including physiotherapists, nutritionists, and psychology-trained personnel. The exercise component will include endurance, resistance, and breathing exercises tailored to the individual patient's clinical condition. Endurance training will consist of progressively increasing moderate-intensity continuous training, with intensity adjusted according to patient performance and perceived exertion using the Borg scale. Resistance exercises will involve different upper- and lower-limb muscle groups, with progressive workload adjustments based on individual performance. The program will include two to three supervised training sessions per week, with a minimum frequency of three exercise sessions per week specified for the overall program. Exercise rehabilitation may be delivered either in a hospital-based or home-based setting according to patient preference and availability. Hospital-based exercise sessions will be conducted in the hospital gym. For patients following the home-based program, the hospital-based intervention will be adapted while maintaining the same overall duration, therapeutic goals, and monitoring approach. Outdoor walking may replace treadmill- or cycle-based aerobic exercise when equipment is unavailable, while resistance exercises will be performed using resistance bands provided by the study center. Educational materials, video demonstrations, and monitoring devices will be provided when appropriate. The nutritional component will consist of an individualized dietary management plan based on dietary habits, medical conditions, and nutritional status. A balanced food-based intervention will be prescribed to meet estimated caloric and nutritional requirements. A daily protein intake of 1.5-2.0 g/kg of ideal body weight will be recommended, and whey protein supplementation may be prescribed when needed. Participants will also receive instruction on anxiety-reducing strategies, including imagery, visualization, and deep-breathing techniques. The primary objective of the study is to assess the feasibility of the 4-week multimodal rehabilitation program. Feasibility will be evaluated according to five predefined criteria: at least 50% of eligible patients agree to participate; at least 80% of enrolled patients adhere to the program; at least 80% of participants complete an outcome assessment after rehabilitation; the proportion of missing data among patients completing outcome assessments is below 10%; and no serious adverse events related to the rehabilitation program occur. The intervention will be considered feasible only if all five predefined criteria are met. Adherence will be defined as completion of at least 80% of the planned intervention components, including exercise sessions, nutritional consultations, and psychological support sessions. For hospital-based rehabilitation, adherence will be documented by the rehabilitation team, while adherence to the home-based program will be assessed using patient diaries reviewed during regular telephone contacts. An exploratory subgroup analysis will compare feasibility outcomes between hospital-based and home-based rehabilitation. Secondary objectives will evaluate functional recovery following surgery. Outcomes will include the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Physical Health Summary Score and Mental Health Summary Score, the 6-minute walk test (6MWT), and the Duke Activity Status Index (DASI). Recovery will be assessed in relation to preoperative values and predefined minimal important differences. Assessments will be performed preoperatively, at hospital discharge, at the end of the 4-week rehabilitation program, and 90 days after surgery. In patients with malignancy who are candidates for adjuvant treatment, time to return to intended oncologic treatment (RIOT) will also be evaluated. Safety will be assessed by monitoring, recording, and analyzing adverse events occurring during the study, with particular attention to events potentially related to exercise training, nutritional intervention, or psychological support. Routine clinical assessments performed as part of standard postoperative care will also contribute to the safety evaluation. The planned sample size is 40 participants. Assuming an expected adherence rate of 80%, this sample size allows adherence to be estimated with a 95% confidence interval of approximately ±12 percentage points and is considered appropriate for the pilot feasibility objective of the study. Enrollment is planned over 12 months, the rehabilitation intervention will last 4 weeks, and participants will be followed for up to 3 months.