Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Anti-Infective Agents

All Drugs and Chemicals

Central Nervous System Depressants

Analgesics

Anti-Bacterial Agents

Antibiotics, Antitubercular

Ethanol

Opiate Alkaloids

Perioperative care for colorectal cancer cancer is managed according to current hospital clinical practice.

Perioperative care for colorectal cancer surgery is managed according to ERAS protocol.

In colorectal cancer surgery, the ERAS protocol involves an accurate interview with the patient in the preoperative phase aimed at smoking and alcohol cessation, the reduction of preoperative fasting with administration of oral carbohydrates before surgery, use of intestinal preparation for selected cases only (rectal surgery), the prophylaxis of thromboembolism, a correct antibiotic prophylaxis, the prevention of intraoperative hypothermia, prevention of volume overload, preference for minimally invasive surgery, prevention of postoperative nausea and vomiting, very limited use of the nasogastric tube, early removal of the urinary catheter, multimodal analgesia to minimize opiate consumption, early postoperative mobilization and early post-operative feeding, to promote rapid recovery of gastro-intestinal functions.

ERAS protocol

Giovannino Ciccone, MD

The study assesses the impact on quality of care of implementing the ERAS (Enhanced Recovery After Surgery) protocol for colorectal cancer surgery in the network of public hospitals in the Regione Piemonte (North-West Italy). Every hospital is a cluster entering the study treating patients according to its current clinical practice. On the basis of a randomized order, each hospital switches from current clinical practice to the adoption of the ERAS protocol.

ERAS (Enhanced Recovery After Surgery) protocol is a multimodal perioperative care pathways designed to achieve early recovery after surgical procedures by maintaining preoperative organ function and reducing the profound stress response following surgery. Even if efficacy and safety of ERAS protocol in colorectal surgery is well-established in the literature, its implementation is limited to few selected centres in Piemonte. The aim of the study is to extend the implementation of the ERAS protocol to whole regional network of hospitals. Specific objectives are to estimate its impact on different dimensions of quality of care, including length of stay, complications and patient satisfaction, and to identify possible barriers or facilitating factors.

A stepped-wedge cluster randomized clinical trial. Each center starts as control group (usual care) and switch to experimental group (ERAS protocol implementation) according to a randomized order.

ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Colorectal Cancer Surgery

ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Colorectal Cancer Surgery. A Stepped-wedge Cluster Randomized Clinical Trial

Anonymised data can be made available upon reasonable request, with appropriate human research ethics approvals and data transfer agreements in place.

Mean length of stay calculated as difference between date of discharge and date of admission of the hospitalization for surgery, excluding length of stay \>94th percentile of the expected distribution (expected 22 days).

Rate of patients with a length of stay \>22 days

Score of quality of recovery at 24 hours after surgery, assessed with the questionnaire Quality of Recovery (QoR-15), a 15-items instrument, with responses recorded on a 11-point Likert-type scale form 0 (worst scenario) to 10 (best scenario) and an overall score ranging from 0 (poor recovey) to 150 (excellent recovery).

A visual analogue scale (VAS), ranging from 0 (worst imaginable health state) to 10 (worst imaginable health state) is also supplied as summary evaluation.

Rate of surgical and medical complication after surgery For surgical complications: Comprehensive Complication Index

Rate of transfers to intensive care unit after surgery

Rate of emergency visit in the first month after discharge

Rate of new admissions in the first month after discharge

Rate of reintervention in the first month after surgery, excluding planned interventions

Score of patients' satisfaction measured 2 weeks after discharge, assessed with the questionnaire Surgical Satisfaction Questionnaire (SSQ8) supplied by telephone. SSQ8 is a 8-items instrument, with responses recorded on a 5-point Likert-type scale from 0 (worst scenario) to 4 (best scenario) and an overall score ranging from 0 (very unsatisfied) to 32 (very satisfied).

Mean healthcare costs from pre admission visit to 30 days after discharge

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Ministry of Health, Italy

Regione Piemonte

Ospedale Santa Croce-Carle Cuneo

Surgeon

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Perioperative care for hysterectomy of benign or malignant tumors of the uterus is managed according to current hospital clinical practice.

Perioperative care for hysterectomy of benign or malignant tumors of the uterus is managed according to ERAS protocol.

In gynecological surgery, the ERAS protocol involves an accurate interview with the patient in the preoperative phase aimed at smoking and alcohol cessation, the reduction of preoperative fasting, the omission of intestinal preparation, the prophylaxis of thromboembolism, a correct antibiotic prophylaxis, the prevention of intraoperative hypothermia, prevention of volume overload, prevention of postoperative nausea and vomiting, very limited use of the nasogastric tube, early removal of the urinary catheter, multimodal analgesia to minimize opiate consumption, early postoperative mobilization and early post-operative feeding, to promote rapid recovery of gastro-intestinal functions.

Andrea Puppo, MD

Marco Camanni, MD

The study assesses the impact on quality of care of implementing the ERAS (Enhanced Recovery After Surgery) protocol for hysterectomy of benign or malignant tumors of the uterus in the network of public hospitals in the Regione Piemonte (North-West Italy). Every hospital is a cluster entering the study treating patients according to its current clinical practice. On the basis of a randomized order, each hospital switches from current clinical practice to the adoption of the ERAS protocol.

ERAS (Enhanced Recovery After Surgery) protocol is a multimodal perioperative care pathways designed to achieve early recovery after surgical procedures by maintaining preoperative organ function and reducing the profound stress response following surgery. Even if efficacy and safety of ERAS protocol in gynaecological surgery is well-established in the literature, its implementation is limited to few selected centres in Piemonte. The aim of the study is to extend the implementation of the ERAS protocol to whole regional network of hospitals. Specific objectives are to estimate its impact on different dimensions of quality of care, including length of stay, complications and patient satisfaction, and to identify possible barriers or facilitating factors.

ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Hysterectomy.

ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Hysterectomy of Benign or Malignant Tumors of the Uterus. A Stepped-wedge Cluster Randomized Clinical Trial.

Mean length of stay calculated as difference between date of discharge and date of admission of the hospitalization for surgery, excluding length of stay \>12 days (98th percentile of the expected distribution).

Rate of patients with a length of stay \>12 days

Score of quality of recovery at 24 hours after surgery, assessed with the questionnaire Quality of Recovery (QoR-15), a 15-items instrument, with responses recorded on a 11-point Likert-type scale form 0 (worst scenario) to 10 (best scenario) and an overall score ranging from 0 (poor recovery) to 150 (excellent recovery).

A visual analogue scale (VAS), ranging from 0 (worst imaginable health state) to 10 (worst imaginable health state) is also supplied as summary evaluation.

Martini Hospital, Turin, Italy

Ospedale Regina Montis Regalis

Gynecologists

Symptoms and General Pathology

Carcinoma

Recurrence

Postoperative Complications

Intraoperative Complications

Disease Progression

Rectal Neoplasms

Patients undergo robot-assisted resections.

Patients undergo laparoscopic resections.

Arm I: Robot-assisted resection using da vinci system.

Robot-assisted resection

Arm II: Traditional laparoscopic resection.

Laparoscopic resection

Jianmin Xu, Ph.D., M.D.

The purpose of this study is to evaluate the safety and oncological feasibility of robot-assisted surgery for mid/low rectal carcinoma compared with laparoscopic surgery.

Laparoscopic surgery as the treatment for colon cancer has been widely recognized. But its use for rectal cancer is still controversial. Previous trials have shown that although the long-term survival outcomes were similar, laparoscopic surgery did not reach the non-inferiority in terms of local tumor radical resection, compared with open surgery. Robotic techniques are considered to improve the quality of surgery with three-dimensional vision, stable camera platform and flexible robotic arms. Meta-analyses have shown that compared with laparoscopic surgery, robotic surgery could improve surgical quality in terms of open conversion, circumferential resection margin, postoperative complications, postoperative recovery, and quality of life, with similar long-term survival. However, these evidences mainly came from retrospective studies and small-scale randomized controlled trials with low quality. There still needs high-quality clinical trials to confirm the advantages of robotic surgery for rectal cancer.

Robot-assisted Versus Laparoscopic Surgery for Mid/Low Rectal Cancer

Robot-assisted Versus Laparoscopic Surgery for Mid/Low Rectal Cancer (REAL): A Multicenter Randomized Controlled Trial

The proportion of patients with any cancer recurrence in the pelvic or perineal area

The proportion of patients with circumferential resection margin ≤ 1 mm from the tumor

The proportion of patients with any complications occurred within 30 days after surgery

Time from surgery to any recurrence, metastases or death

Time from making skin incision to suturing the incision during the surgery

The proportion of patients with the use of a laparotomy incision for any part of the TME procedure or lymph nodes dissection during the surgery

Blood loss will be measured according to the suction and the weight of wet gauze, and then minus the irrigation.

The proximal/distal resection margin will be reported as "positive" or "negative" to define whether tumor is radically resected. It will be reported according to the post-operative pathology. Details are based on NCCN and Chinese guidelines for colorectal cancer.

The number of lymph node found from the surgical specimen

The postoperative hospital stay is defined as the number of date from the first day after operation to discharge.

This section is assessed using a self-rating scale "International prostate symptom score" (IPSS).

This section is assessed using a self-rating scale "International Index of Erectile Function" (IIEF-5).

This section is assessed using a self-rating scale "Female Sexual Function Index" (FSFI).

Fudan University

Head of Colorectal Surgery

A prospective series of consecutive patients undergoing elective colorectal surgery completing a standardized Enhanced Recovery Program (ERP) protocol at the S. Anna University Hospital in Ferrara (Italy) in 2013-2015

A retrospective series of consecutive patients operated at the same hospital (S. Anna University Hospital in Ferrara), in the same period of time (2013-2015), but with a traditional perioperative care protocol.

An evidence-based perioperative care approach, involving a multidisciplinary team work including surgeons, anaesthesiologists, dieticians, and nurses, which aim to reduce the surgical stress and metabolic responses as well as organ dysfunction, thus leading to a faster recovery after surgery

Enhanced Recovery Program (ERP)

Carlo V Feo, MD

Background: A few randomized clinical trials and meta-analysis provide evidence for enhanced recovery programs (ERPs) in colorectal surgery. Most of the evidence, however, relies on non-randomized controlled studies that have control groups being either historical or operated on at different facilities. The aim of this study was to compare a prospective series of patients undergoing elective colorectal surgery according to ERPs, with a coeval retrospective series of patients undergoing elective colorectal surgery in a different ward at the same hospital.

The primary outcome was hospital length of stay, which was used as a proxy of functional recovery. Secondary outcomes included: postoperative complications, readmission rate, mortality, and adherence to the protocol.

Materials and Methods: A prospective series of consecutive patients (N = 100) undergoing elective colorectal resection completing a standardized ERP in 2013-2015 (ERP Group) will be compared to patients (N = 100) operated at the same institution in the same period with a traditional perioperative care protocol (Non-ERP group). Despite different surgeons and ward nurses, the two groups shared the same anaesthesiologists and were located in separate wards. The exclusion criteria were: \>80 years old, ASA score of IV, a stage IV TNM, and diagnosis of inflammatory bowel disease.

1. Introduction

   One of the most important achievements in modern surgery is the implementation in perioperative care of Enhanced Recovery Programs (ERPs), pioneered by Henrik Kehlet in the mid-1990s \[1\]. ERP is an evidence-based perioperative care approach, involving a multidisciplinary team work including surgeons, anaesthesiologists, dieticians, and nurses, which aim to reduce the surgical stress and metabolic responses as well as organ dysfunction, thus leading to a faster recovery after surgery \[2\].

   Such a team works with a multimodal approach to perioperative care, sharing all the endpoints of management throughout the perioperative phases, and acting in close relationship with the patient along his/her "journey in hospital". In other words, each perioperative phase comprises several core items based on solid scientific evidence that are delivered by different professionals in different parts of the hospital \[2\].

   A few randomized clinical trials and meta-analysis provide evidence in the literature for the benefits of ERPs in colorectal surgery \[3-6\]. Most non-randomized controlled studies have compared patients undergoing colorectal enhanced recovery surgery with controls being either historical groups or patients operated on at different hospitals \[7-9\].

   In a previous investigation, the investigators showed the benefits of implementing an ERP in elective colorectal surgery by comparing a prospective series of 100 patients operated on receiving enhanced recovery care (ERP group), with a retrospective cohort of 100 patients operated on by the same professionals at the same institution before the introduction of the ERP (Pre-ERP group) \[10\].

   The present study aims to investigate the differences between a prospective series of patients undergoing elective colorectal surgery following an ERP and a retrospective cohort of patients operated on with traditional perioperative care in the same period by a different team of surgeons and hospitalized in a different ward of the same hospital.
2. Materials and Methods

The study was designed as a prospective cohort with retrospective coeval control. A prospective series of 100 consecutive patients undergoing elective colorectal surgery completing a standardized ERP protocol at the S. Anna University Hospital in Ferrara (Italy) in 2013-2015 (ERP group), was compared to a retrospective series of 100 consecutive patients operated at the same hospital, in the same period of time, but with a traditional perioperative care protocol (Non-ERP group). Despite different surgeons and ward nurses, the two groups of patients shared the same anaesthesiologists and were located in two separate wards.

In 2012 the enhanced recovery team was assembled, the ERP protocol was built up, according to the fast-track protocol proposed by Kehlet and Wilmore \[11\], and periodical audits were then performed. Eligible for this study were all patients between 18 and 80 years old scheduled for elective colorectal resection. Exclusion criteria in both study groups were: age \> 80 years old, American Society of Anaesthesia (ASA) score IV, TNM stage IV, and diagnosis of inflammatory bowel disease. Discharging criteria were also the same for both groups: 1) free oral diet, 2) complete intestinal function recovery (passage of flatus and stool), 3) dynamic pain control (Numerical Rate Scale - NRS ≤ 3) by oral analgesia, 4) independent walking, 5) no signs of infection \[10\].

The study protocol was approved by the local Ethics Committee (Ethical Committee for Human Subject Research study number 52-2011), it complies with the Declaration of Helsinki, and all patients provided written informed consent The primary outcome of this study was the length of stay (LoS) in the hospital, adopted as a proxy of functional recovery. Secondary outcomes were: postoperative complications, readmission rate, mortality, and adherence to the protocol.

All complications were recorded until 30 days after surgery, as well as mortality and hospital readmission. To evaluate adherence to the protocol, all ERP items were prospectively collected, recorded and checked by an independent observer using a detailed care program for each postoperative day. The grading of complications was defined according to a validated classification \[12\].

Data were collected prospectively for patients in the ERP group and retrieved from a prospectively maintained database for those in the Non-ERP group.

Surgery was preferably performed by laparoscopy, but alternative approaches were allowed and discussed with patients. A converted laparoscopy was defined as an unplanned extension of the surgical incision (either a median or a transverse suprapubic incision). All operations were performed by surgeons experienced in colorectal surgery and advanced laparoscopy (CVF, GA).

2.1 ERP Group Patients received extensive preoperative counselling about protocol items, all phases of perioperative care, and discharge criteria, along with an illustrated booklet conceived by the multidisciplinary team. The patients were motivated to adhere to protocol items by members of the team throughout the preoperative and postoperative phases and were informed about the daily objectives to be achieved. Incentive spirometers were provided preoperatively and patients were instructed for perioperative breathing exercises.

A normal meal was allowed on the day before surgery; a carbohydrate loaded drink was prescribed in the evening (100 grams of maltodextrin in 800 ml liquid drink) and at least two hours (50 grams of maltodextrin in 400 ml liquid drink) before surgery. No patient was prescribed mechanical bowel preparation.

The nasogastric tube (NGT) and bladder catheter were removed at the end of the procedure and within the second postoperative day \[13\], respectively, whereas abdominal drains were selectively used.

Postoperative pain control was achieved with thoracic epidural analgesia within the first three postoperative days and with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) or paracetamol thereafter. Resumption of liquid and solid diets and discontinuation of intravenous fluids were all achieved within the first and the second postoperative day. Patients were out of bed on postoperative day one and encouraged by nurses to deambulate according to a predefined schedule.

The anaesthetic protocol was standardized as previously described elsewhere \[10\]. In brief, a blended anaesthesia was performed with short-acting anaesthetic agents and mid-thoracic epidural intraoperative analgesia. Attention was put on maintaining normothermia with forced air warming devices during surgical procedures and a multimodal approach to prevent PostOperative Nausea and Vomiting (PONV) was pursued. Intravenous fluid overload was avoided.

2.2 Non-ERP Group Patients were treated according to traditional perioperative care principles in use at the institution. Specifically, on the day before surgery patients fasted from midnight, received no carbohydrate loaded drink, and performed a mechanical bowel preparation.

An opioid-based anaesthesia with or without thoracic epidural was used, while postoperative pain control was achieved by intravenous opioids, thoracic epidural or NSAIDs.

The NGT was removed at the restoration of intestinal activity when oral feeding was resumed, while the abdominal drain was removed at bowel movements.

No predefined schedule was followed for patients' mobilization and the bladder catheter was removed at full mobilization and after discontinuation of intravenous fluids.

Patients received no daily goal assignments or specific preoperative counselling.

In order to determine in between groups perioperative care differences, an independent observer reviewed the medical charts of all patients to evaluate the adherence to the 21 protocol items.

2.3 Statistical Analysis Clinical parameters were expressed as median (interquartile range - IQR 25-75) and mean ± standard deviation according to distribution assessed by Shapiro-Wilk test. Categorical data were presented as numbers. Clinical and pathological variables were analysed with Chi-square, t-student, and Mann-Whitney tests as appropriate. The Kaplan-Meier test method and Log-Rank test were used to compare duration of surgical operation, time to functional recovery and hospital LoS between groups. A P value of less than 0.05 was considered statistically significant. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp. Armonk, NY: IBM Corp.).

Enhanced Recovery Program in Laparoscopic Colorectal Surgery: an Observational Controlled Trial

There is not a plan to make IPD available.

The postoperative hospital LOS, proxy of functional recovery, is defined as the number of days from the date of surgical operation to the date of hospital. Patients in both study groups wil be discharged from the hospital upon reaching all predefined discharged criteria. For the ERP group it is estimated a 4 to 5-day hospital LOS according to the protocol, while in the traditional group an 8 to 10-day hospital stay is expected.

The ERP protocol includes 21 items; the adherence to the items will be evaluated for each patient in the postoperative period. Then, the adherence rate will be calculated.

University Hospital of Ferrara

Gland and Hormone Related Diseases

Rare Diseases

Behaviors and Mental Disorders

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Quality of Life

Nicolò Pecorelli, Surgeon

This is a prospective single-center observational study with the mail objective to identify specific subgroups of patients planned for pancreatic resection, at high risk for postoperative morbidity and impaired recovery through preoperative screening of physical, functional, nutritional and psychological risk factors using patient reported questionnaires and performance tests.

Consecutive patients planned for pancreatic resection will be enrolled to screen for physical, functional, nutritional and psychological risk factors. The study duration is 3 years: 2 years of recruitment and 1 year of follow-up.

The findings of the present study will enable researchers to identify specific risk categories to plan personalized prehabilitation programs and modulate oncologic treatment strategies in cancer patients planned for pancreatic surgery.

Patients undergoing pancreatic surgery, even treated in high-volume centers, still experience significant postoperative morbidity and full recovery after surgery takes longer than expected, delaying access to adjuvant oncologic treatment and influencing disease prognosis and patient quality of life. Patient health status at the time of surgery represents a major determinant of postoperative recovery. However, it is often evaluated with traditional measures such as performance status and comorbidity indices, which are frequently inaccurate and fail to capture the multiple dimensions of health and the patients' perspective.

Recent literature promotes the adoption of patient reported outcome measures (PROMs) to assess health across different domains (e.g. symptoms, functional status, well-being). These measures generally take the form of questionnaires and allow a more holistic understanding of patient's health and how surgery can affect different aspects of it. Thus, PROMs could be used as tools to identify patients at higher risk for postoperative adverse events or prolonged recovery.

Once higher risk profile patients have been identified, they could be referred to a for a personalized optimization program before surgery (i.e. prehabilitation). In fact, a few studies have recently enrolled high-risk patients candidate for major elective abdominal surgery in preoperative programs including multimodal interventions (e.g. physical activity, nutrition, mental exercise) resulting in decreased postoperative complications and earlier return of function. Optimizing preoperative status may reduce postoperative complications, enhance postoperative functional recovery and lead to shorter hospital stay, fewer readmissions, less time off work and improve patient perceived health-related quality of life.

Since high-risk patients benefit more from preoperative optimization strategies, and the implementation of a prehabilitation program is costly and resource-intensive, identifying patients at higher risk for postoperative poor outcomes is a key aspect. Unfortunately, there is no consensus on the best method to define these patients in the context of pancreatic surgery.

The main objective of this project is to identify specific subgroups of patients planned for pancreatic resection, at high risk for postoperative morbidity and impaired recovery through preoperative screening of physical, functional, nutritional and psychological risk factors using patient reported questionnaires and performance tests. The findings of the present study will enable researchers to identify specific risk categories to plan personalized prehabilitation programs and modulate oncologic treatment strategies in cancer patients planned for pancreatic surgery.

PRO-PANC1 is a prospective single-center observational study including consecutive patients planned for pancreatic resection to screen for physical, functional, nutritional and psychological risk factors.

Patients will be enrolled for 24 months and evaluated at the pre-admission visit (usually 1-2 weeks before surgery), at time of admission (i.e. the day before surgery), during hospital stay and trough a follow-up at 30 and 90 days, 6 and 12 monts after surgery. A navigator nurse who is already involved in patient follow-up after surgery will prompt patients to complete the questionnaires. There will be no additional visits or costs for patients and healthcare personnel in this activity.

PROMS (PATIENT REPORTED OUTCOMES MEASURES)

At their pre-admission visit, within 4 weeks before surgery, enrolled patients after signing the informed consent, will be asked to fill the following self-reported questionnaires:

* "Patient Reported Outcomes Measurement Information System (PROMIS) 29+2 Profile v2.1 (PROPr)", which is a flexible set of tools designed to measure self-reported physical, mental and social health and wellbeing which has been constructed and validated rigorously. It contains items from the following domains: depression, anxiety, physical function, pain interference, fatigue, sleep disturbance and ability to participate in social roles and activities.
* Duke Activity Status Index (DASI) to evaluate patient physical status.
* Risk Analysis Index (RAI-C) to evaluate frailty, comorbidities and performance status.
* Patient Health Engagement scale (PHE-s) to assess patient engagement in their process of care based on their emotional and cognitive status.
* World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) - 12 items, a generic instrument to measure health and disability covering 6 domains of functioning.

PHYSICAL EVALUATION Physical performance testing will only be performed for a subgroup of patients in accordance with the availability of the physiotherapist and of the involved physician. Physical status will be evaluated by performace tests at the time of hospital admission (i.e. the day before surgery) for the baseline evaluation and at 30- days after surgery during the routine outpatient follow- up visit. The patient, either already admitted to the surgical ward, or during the outpatient evaluation will undergo testing with the physiotherapist in a dedicated area within the hospital (i.e. rehabilitation gym).

Performance tests will include: six-minute walk test, time up and go test, strength tests (target muscles will be the quadriceps and the handrip muscles: in both cases a specific dynamometer will be utilized) and the Modified Iowa Level of Assistance Scale (MILAS) evaluation.

In a subgroup of 100 cancer patients undergoing major pancreatic resection (pancreaticoduodenectomy and total pancreatectomy), preoperative cardiopulmonary exercise testing (CPET) will be administered. CPET is a non-invasive, dynamic test that provides a global assessment of the integrative responses to exercise.

NUTRITIONAL EVALUATION A baseline nutritional assessment will be performed at the pre-admission office visit or at the time of hospital admission (i.e. the day before surgery) by a study investigator. If the patient is already hospitalized, the evaluation will be performed at the patient bedside. The evaluation will include a nutrition history (e.g. weight loss, daily intake), measurement of anthropometric parameters including body weight (kg), height (cm), and body mass index (kg/m2). The Mini Nutritional Assessment (MNA) tool will be used to screen patients for nutrition risk. Standard biochemical markers of malnutrition and inflammation, including albumin, total proteins, total lymphocyte count, and C-reactive protein will be measured in all patients as part of the routine preoperative testing.

In a subgroup of patients, in accordance with the availability of the nutritionist, multi-frequency bioelectrical impedance vector analysis (BIVA) will be used to estimate total body water (TBW), extra-cellular water (ECW), fat free mass (FFM), fat mass (FM), body cell mass (BCM) and phase angle (PhA). This analysis will be performed at the time of the patient pre-admission visit or when the patient is admitted to the ward.

RADIOLOGIC EVALUATION Preoperative imaging (i.e. CT scan, MRI) performed within 30 days before surgery will be reviewed by a radiologist to evaluate pancreatic parenchyma morphological parameters with a potential impact on postoperative outcomes such as pancreatic duct size, pancreatic gland diameter, and fatty infiltration. Body composition parameters will also be evaluated including quantification of skeletal muscle area, visceral fat area, and subcutaneous fat area.

RISK SCORE ASSESSMENT Using a digital ecosystem platform, all information will be automatically captured and stored in the pancreatic disease institutional registry, in addition to other clinical information including laboratory tests, diagnostic imaging, pathology, and clinical history.

PROMS validity will be assessed in the context of pancreatic surgery according to the COSMIN recommendations for the design of the studiesy on measurement properties.

After evaluating the performance of each screening test, a practical risk scoring system for postoperative outcomes will then be developed based on regression models.

The newly developed score will then be released on a web page and app to allow researchers and clinicians to individually compute the score preoperatively to both inform patients of risks and to modify perioperative treatment strategies.

SAMPLE SIZE AND ANALYSIS The number of pancreatic resections at the San Raffaele Hospital Division of Pancreatic Surgery is around 330 per year. We assume that the rate of patients at high risk to develop postoperative complication is about 30%. Considering an overall rate of patients' refusal/not satisfying inclusion criteria/not performing physical or nutritional evaluation of 15%, we expect to enroll 561 patients in 24 months to have a hypothetical overall number of high risk patients of 168. After evaluating the performance of each screening test, a practical risk scoring system for postoperative outcomes will then be developed based on regression models.

Patient Reported Outcomes Measures to Predict Pancreatic Surgery Outcomes

The PRO-PANC1 Project: Patient Reported Outcomes Measures to Predict Pancreatic Surgery Outcomes

Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the "ideal" surgical outcome. TO is defined by the absence of clinically-relevant postoperative pancreatic fistula, bile leak, postpancreatectomy hemorrhage, severe complications (Clavien-Dindo ≥III) including mortality, and readmission.

The primary outcome will be the failure to achieve a textbook outcome.

Postoperative complications occurring during the index admission or in a subsequent readmission, when related to surgery, will be recorded up to 90 days after surgery and graded by severity using the Dindo-Clavien classification and the Comprehensive Complication index (CCI).

The Dindo-Clavien system grades complications according to the therapy needed for treatment: Grade I, are complications that require bedside management; Grade II, are complications that require pharmacologic treatment; Grade III, are complications that require surgical or radiologic intervention and; Grade IV, are complications that require intensive care treatment. Dindo-Clavien Grade III or above are considered severe postoperative complications.

The CCI, derived from the Dindo-Clavien system, is a validated metric summarizing the complete spectrum of complications that occurred and their severity in a single score ranging from 0 to 100.

Occurrence of clinically-relevant postoperative pancreatic fistula defined as grade B or C POPF according to the 2016 International Study Group in Pancreatic Surgery (ISGPS) definition.

Time to functional recovery will be measured by subtracting the date of surgery from the date when participants achieve standardized criteria (tolerance of oral intake, recovery of lower gastrointestinal function, adequate pain control on oral analgesia, ability to mobilize and self-care and no evidence of untreated medical problems).

Generic health-related quality of life will be measured using PROMIS-29+2, a questionnaire designed to measure self-reported physical, mental and social health status. It contains 29 questions covering seven domains of health. Questions are ranked on a 5-point Likert Scale. Each domain (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities) is scored from 4 to 20. For negative domains (i.e. Depression), lower scores represent better outcomes, higher scores represent worse outcomes. For positive domains (i.e. Physical function), lower scores represent worse outcomes, higher scores represent better outcomes.

Clinically meaningful minimally important differences for PROMIS scores are not established for our patient population. Difference in PROMIS scores for health domains between baseline and postoperative time points (30 and 90 days) will be considered to evaluate recovery after surgery.

Self-reported activity status will be measured using the Duke Activity Status Index (DASI), a brief questionnaire designed to assess physical function and predict exercise capacity (peak oxygen uptake). Participants are asked to respond whether they are able to perform 12 listed activities of various intensities (ambulation, household tasks, personal care and leisure activities). A specific score is given for each positive answer. The possible total score range from 0 to 58. 0 corresponds to no activity (worse outcome); 58 corresponds to performance of all activities (best outcome).

This Secondary outcome includes the return at 30 days after surgery to preoperative exercise capacity as measured by the Six Minute Walk Test (6MWT).

The 6MWT measures the total distance covered in 6 minutes of maximal walking effort.

Patients will be considered to have recovered their exercise capacity when postoperative distance is within 20 meters of preoperative value or above.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Colorectal Cancer Surgery	NCT04037787	Colorectal Canc... Quality Improve... Perioperative C... Recovery of Fun...	ERAS protocol	18 Years -	Ospedale Santa Croce-Carle Cuneo
ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Hysterectomy.	NCT04063072	Uterine Neoplas...	ERAS protocol	18 Years -	Ospedale Regina Montis Regalis
Robot-assisted Versus Laparoscopic Surgery for Mid/Low Rectal Cancer	NCT02817126	Rectal Carcinom...	Robot-assisted ... Laparoscopic re...	18 Years - 80 Years	Fudan University
Enhanced Recovery Program in Laparoscopic Colorectal Surgery: an Observational Controlled Trial	NCT04378465	Colorectal Surg... Recovery of Fun...	Enhanced Recove...	18 Years - 80 Years	University Hospital of Ferrara
Patient Reported Outcomes Measures to Predict Pancreatic Surgery Outcomes	NCT04431076	Pancreatic Canc... Patient Reporte... Quality of Life Pancreatectomy Nutritional Sta... Recovery of Fun...		18 Years -	IRCCS San Raffaele
ERAS (Enhanced Recovery After Surgery) Protocol Implementation in Piedmont Region for Hysterectomy.	NCT04063072	Uterine Neoplas...	ERAS protocol	18 Years -	Ospedale Regina Montis Regalis

Spots Global Cancer Trial Database for recovery of function