<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04431076</url>
  </required_header>
  <id_info>
    <org_study_id>PRO-PANC1</org_study_id>
    <nct_id>NCT04431076</nct_id>
  </id_info>
  <brief_title>Patient Reported Outcomes Measures to Predict Pancreatic Surgery Outcomes</brief_title>
  <acronym>PRO-PANC1</acronym>
  <official_title>The PRO-PANC1 Project: Patient Reported Outcomes Measures to Predict Pancreatic Surgery Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massimo Falconi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS San Raffaele</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective single-center observational study with the mail objective to identify&#xD;
      specific subgroups of patients planned for pancreatic resection, at high risk for&#xD;
      postoperative morbidity and impaired recovery through preoperative screening of physical,&#xD;
      functional, nutritional and psychological risk factors using patient reported questionnaires&#xD;
      and performance tests.&#xD;
&#xD;
      Consecutive patients planned for pancreatic resection will be enrolled to screen for&#xD;
      physical, functional, nutritional and psychological risk factors. The study duration is 3&#xD;
      years: 2 years of recruitment and 1 year of follow-up.&#xD;
&#xD;
      The findings of the present study will enable researchers to identify specific risk&#xD;
      categories to plan personalized prehabilitation programs and modulate oncologic treatment&#xD;
      strategies in cancer patients planned for pancreatic surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients undergoing pancreatic surgery, even treated in high-volume centers, still experience&#xD;
      significant postoperative morbidity and full recovery after surgery takes longer than&#xD;
      expected, delaying access to adjuvant oncologic treatment and influencing disease prognosis&#xD;
      and patient quality of life. Patient health status at the time of surgery represents a major&#xD;
      determinant of postoperative recovery. However, it is often evaluated with traditional&#xD;
      measures such as performance status and comorbidity indices, which are frequently inaccurate&#xD;
      and fail to capture the multiple dimensions of health and the patients' perspective.&#xD;
&#xD;
      Recent literature promotes the adoption of patient reported outcome measures (PROMs) to&#xD;
      assess health across different domains (e.g. symptoms, functional status, well-being). These&#xD;
      measures generally take the form of questionnaires and allow a more holistic understanding of&#xD;
      patient's health and how surgery can affect different aspects of it. Thus, PROMs could be&#xD;
      used as tools to identify patients at higher risk for postoperative adverse events or&#xD;
      prolonged recovery.&#xD;
&#xD;
      Once higher risk profile patients have been identified, they could be referred to a for a&#xD;
      personalized optimization program before surgery (i.e. prehabilitation). In fact, a few&#xD;
      studies have recently enrolled high-risk patients candidate for major elective abdominal&#xD;
      surgery in preoperative programs including multimodal interventions (e.g. physical activity,&#xD;
      nutrition, mental exercise) resulting in decreased postoperative complications and earlier&#xD;
      return of function. Optimizing preoperative status may reduce postoperative complications,&#xD;
      enhance postoperative functional recovery and lead to shorter hospital stay, fewer&#xD;
      readmissions, less time off work and improve patient perceived health-related quality of&#xD;
      life.&#xD;
&#xD;
      Since high-risk patients benefit more from preoperative optimization strategies, and the&#xD;
      implementation of a prehabilitation program is costly and resource-intensive, identifying&#xD;
      patients at higher risk for postoperative poor outcomes is a key aspect. Unfortunately, there&#xD;
      is no consensus on the best method to define these patients in the context of pancreatic&#xD;
      surgery.&#xD;
&#xD;
      The main objective of this project is to identify specific subgroups of patients planned for&#xD;
      pancreatic resection, at high risk for postoperative morbidity and impaired recovery through&#xD;
      preoperative screening of physical, functional, nutritional and psychological risk factors&#xD;
      using patient reported questionnaires and performance tests. The findings of the present&#xD;
      study will enable researchers to identify specific risk categories to plan personalized&#xD;
      prehabilitation programs and modulate oncologic treatment strategies in cancer patients&#xD;
      planned for pancreatic surgery.&#xD;
&#xD;
      PRO-PANC1 is a prospective single-center observational study including consecutive patients&#xD;
      planned for pancreatic resection to screen for physical, functional, nutritional and&#xD;
      psychological risk factors.&#xD;
&#xD;
      Patients will be enrolled for 24 months and evaluated at the pre-admission visit (usually 1-2&#xD;
      weeks before surgery), at time of admission (i.e. the day before surgery), during hospital&#xD;
      stay and trough a follow-up at 30 and 90 days, 6 and 12 monts after surgery. A navigator&#xD;
      nurse who is already involved in patient follow-up after surgery will prompt patients to&#xD;
      complete the questionnaires. There will be no additional visits or costs for patients and&#xD;
      healthcare personnel in this activity.&#xD;
&#xD;
      PROMS (PATIENT REPORTED OUTCOMES MEASURES)&#xD;
&#xD;
      At their pre-admission visit, within 4 weeks before surgery, enrolled patients after signing&#xD;
      the informed consent, will be asked to fill the following self-reported questionnaires:&#xD;
&#xD;
        -  &quot;Patient Reported Outcomes Measurement Information System (PROMIS) 29+2 Profile v2.1&#xD;
           (PROPr)&quot;, which is a flexible set of tools designed to measure self-reported physical,&#xD;
           mental and social health and wellbeing which has been constructed and validated&#xD;
           rigorously. It contains items from the following domains: depression, anxiety, physical&#xD;
           function, pain interference, fatigue, sleep disturbance and ability to participate in&#xD;
           social roles and activities.&#xD;
&#xD;
        -  Duke Activity Status Index (DASI) to evaluate patient physical status.&#xD;
&#xD;
        -  Risk Analysis Index (RAI-C) to evaluate frailty, comorbidities and performance status.&#xD;
&#xD;
        -  Patient Health Engagement scale (PHE-s) to assess patient engagement in their process of&#xD;
           care based on their emotional and cognitive status.&#xD;
&#xD;
        -  World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) - 12 items, a&#xD;
           generic instrument to measure health and disability covering 6 domains of functioning.&#xD;
&#xD;
      PHYSICAL EVALUATION Physical performance testing will only be performed for a subgroup of&#xD;
      patients in accordance with the availability of the physiotherapist and of the involved&#xD;
      physician. Physical status will be evaluated by performace tests at the time of hospital&#xD;
      admission (i.e. the day before surgery) for the baseline evaluation and at 30- days after&#xD;
      surgery during the routine outpatient follow- up visit. The patient, either already admitted&#xD;
      to the surgical ward, or during the outpatient evaluation will undergo testing with the&#xD;
      physiotherapist in a dedicated area within the hospital (i.e. rehabilitation gym).&#xD;
&#xD;
      Performance tests will include: six-minute walk test, time up and go test, strength tests&#xD;
      (target muscles will be the quadriceps and the handrip muscles: in both cases a specific&#xD;
      dynamometer will be utilized) and the Modified Iowa Level of Assistance Scale (MILAS)&#xD;
      evaluation.&#xD;
&#xD;
      In a subgroup of 100 cancer patients undergoing major pancreatic resection&#xD;
      (pancreaticoduodenectomy and total pancreatectomy), preoperative cardiopulmonary exercise&#xD;
      testing (CPET) will be administered. CPET is a non-invasive, dynamic test that provides a&#xD;
      global assessment of the integrative responses to exercise.&#xD;
&#xD;
      NUTRITIONAL EVALUATION A baseline nutritional assessment will be performed at the&#xD;
      pre-admission office visit or at the time of hospital admission (i.e. the day before surgery)&#xD;
      by a study investigator. If the patient is already hospitalized, the evaluation will be&#xD;
      performed at the patient bedside. The evaluation will include a nutrition history (e.g.&#xD;
      weight loss, daily intake), measurement of anthropometric parameters including body weight&#xD;
      (kg), height (cm), and body mass index (kg/m2). The Mini Nutritional Assessment (MNA) tool&#xD;
      will be used to screen patients for nutrition risk. Standard biochemical markers of&#xD;
      malnutrition and inflammation, including albumin, total proteins, total lymphocyte count, and&#xD;
      C-reactive protein will be measured in all patients as part of the routine preoperative&#xD;
      testing.&#xD;
&#xD;
      In a subgroup of patients, in accordance with the availability of the nutritionist,&#xD;
      multi-frequency bioelectrical impedance vector analysis (BIVA) will be used to estimate total&#xD;
      body water (TBW), extra-cellular water (ECW), fat free mass (FFM), fat mass (FM), body cell&#xD;
      mass (BCM) and phase angle (PhA). This analysis will be performed at the time of the patient&#xD;
      pre-admission visit or when the patient is admitted to the ward.&#xD;
&#xD;
      RADIOLOGIC EVALUATION Preoperative imaging (i.e. CT scan, MRI) performed within 30 days&#xD;
      before surgery will be reviewed by a radiologist to evaluate pancreatic parenchyma&#xD;
      morphological parameters with a potential impact on postoperative outcomes such as pancreatic&#xD;
      duct size, pancreatic gland diameter, and fatty infiltration. Body composition parameters&#xD;
      will also be evaluated including quantification of skeletal muscle area, visceral fat area,&#xD;
      and subcutaneous fat area.&#xD;
&#xD;
      RISK SCORE ASSESSMENT Using a digital ecosystem platform, all information will be&#xD;
      automatically captured and stored in the pancreatic disease institutional registry, in&#xD;
      addition to other clinical information including laboratory tests, diagnostic imaging,&#xD;
      pathology, and clinical history.&#xD;
&#xD;
      PROMS validity will be assessed in the context of pancreatic surgery according to the COSMIN&#xD;
      recommendations for the design of the studiesy on measurement properties.&#xD;
&#xD;
      After evaluating the performance of each screening test, a practical risk scoring system for&#xD;
      postoperative outcomes will then be developed based on regression models.&#xD;
&#xD;
      The newly developed score will then be released on a web page and app to allow researchers&#xD;
      and clinicians to individually compute the score preoperatively to both inform patients of&#xD;
      risks and to modify perioperative treatment strategies.&#xD;
&#xD;
      SAMPLE SIZE AND ANALYSIS The number of pancreatic resections at the San Raffaele Hospital&#xD;
      Division of Pancreatic Surgery is around 330 per year. We assume that the rate of patients at&#xD;
      high risk to develop postoperative complication is about 30%. Considering an overall rate of&#xD;
      patients' refusal/not satisfying inclusion criteria/not performing physical or nutritional&#xD;
      evaluation of 15%, we expect to enroll 561 patients in 24 months to have a hypothetical&#xD;
      overall number of high risk patients of 168. After evaluating the performance of each&#xD;
      screening test, a practical risk scoring system for postoperative outcomes will then be&#xD;
      developed based on regression models.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 7, 2020</start_date>
  <completion_date type="Anticipated">May 30, 2023</completion_date>
  <primary_completion_date type="Actual">August 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Textbook outcome</measure>
    <time_frame>90 days after surgery</time_frame>
    <description>Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the &quot;ideal&quot; 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.&#xD;
The primary outcome will be the failure to achieve a textbook outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative complications</measure>
    <time_frame>90 days after surgery</time_frame>
    <description>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).&#xD;
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.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pancreatic fistula</measure>
    <time_frame>90 days after surgery</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to functional recovery</measure>
    <time_frame>90 days after surgery</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Generic health related quality of life measured by Patient Reported Outcome Measure Information System (PROMIS)-29+2 Profile version 2.1</measure>
    <time_frame>30 and 90 days after surgery</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self reported physical activity - Duke Activity Status Index (DASI)</measure>
    <time_frame>30 and 90 days after surgery</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Return to preoperative exercise capacity</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>This Secondary outcome includes the return at 30 days after surgery to preoperative exercise capacity as measured by the Six Minute Walk Test (6MWT).&#xD;
The 6MWT measures the total distance covered in 6 minutes of maximal walking effort.&#xD;
Patients will be considered to have recovered their exercise capacity when postoperative distance is within 20 meters of preoperative value or above.</description>
  </secondary_outcome>
  <enrollment type="Actual">560</enrollment>
  <condition>Pancreatic Cancer</condition>
  <condition>Patient Reported Outcome Measures</condition>
  <condition>Quality of Life</condition>
  <condition>Pancreatectomy</condition>
  <condition>Nutritional Status</condition>
  <condition>Recovery of Function</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Consecutive patients planned for pancreatic resection will be enrolled and screened for&#xD;
        physical, functional, nutritional and psychological risk factors. The study duration is 3&#xD;
        years, patients will be recruited for 24 months.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult patients (age &gt; 18 years) with pancreatic, biliary or duodenal diseases&#xD;
             planned for pancreatic resection at San Raffaele Hospital&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with American Society of Anesthesiologists (ASA) health status class 4-5.&#xD;
&#xD;
          -  Patients with co-morbid medical, physical and mental conditions (e.g. dementia,&#xD;
             disabling orthopedic and neuromuscular disease, psychosis), cardiac abnormalities,&#xD;
             severe end-organ disease such as cardiac failure, morbid obesity (BMI &gt;40), anemia&#xD;
             (hematocrit &lt; 30 %) and other conditions interfering with the ability to complete the&#xD;
             performance testing procedures.&#xD;
&#xD;
          -  Inability to read or understand Italian.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicolò Pecorelli, Surgeon</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale San Raffaele IRCCS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS San Raffaele</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Massimo Falconi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Pancreatic cancer</keyword>
  <keyword>Patient Reported Outcome Measures</keyword>
  <keyword>Pancreatectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04431076
org study id: PRO-PANC1
nct id: NCT04431076
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Cohort
time perspective: Prospective
measure: Textbook outcome
time frame: 90 days after surgery
description: 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.
measure: Postoperative complications
time frame: 90 days after surgery
description: 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.
measure: Pancreatic fistula
time frame: 90 days after surgery
description: 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.
measure: Time to functional recovery
time frame: 90 days after surgery
description: 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).
measure: Generic health related quality of life measured by Patient Reported Outcome Measure Information System (PROMIS)-29+2 Profile version 2.1
time frame: 30 and 90 days after surgery
description: 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.
measure: Self reported physical activity - Duke Activity Status Index (DASI)
time frame: 30 and 90 days after surgery
description: 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).
measure: Return to preoperative exercise capacity
time frame: 30 days after surgery
description: 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 pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nicolò Pecorelli, Surgeon
role: Principal Investigator
affiliation: Ospedale San Raffaele IRCCS
facility: 
country: Italy
responsible party type: Sponsor-Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Massimo Falconi
investigator title: Professor
mesh term: Pancreatic Neoplasms