<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/NCT03032679</url>
  </required_header>
  <id_info>
    <org_study_id>1780</org_study_id>
    <nct_id>NCT03032679</nct_id>
  </id_info>
  <brief_title>Pain and Impact of Chronic Pain on Function After Total Knee Replacements</brief_title>
  <official_title>Postoperative Pain Severity, Incidence Of Chronic Pain And Its Impact On Daily Function Following Total Knee Replacements (TKR) At A Tertiary Cancer Institute</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tata Memorial Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tata Memorial Centre</source>
  <oversight_info>
    <has_dmc>Yes</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>
      After Institutional Review Board approval, adult patients scheduled for total knee&#xD;
      arthroplasty (TKA) will be enrolled into the study after obtaining informed consent over a 24&#xD;
      month period. Interim analyses of cases who have completed the 6 month follow up as on 31st&#xD;
      October, 2017 will be analyzed as part of the co- principle investigator's thesis. All&#xD;
      consenting patients will be assessed for pain preoperatively, the first 3 post-operative&#xD;
      days, at 1, 4 and 6 months from the date of surgery. Pain scores will be assessed using the&#xD;
      Numerical Rating Scale during the 3 postoperative days. Pain will be managed by the Acute&#xD;
      Pain Service team as per standard protocols.&#xD;
&#xD;
      The Brief pain inventory (BPI) (short form with translations, obtained with permission from&#xD;
      MD Anderson), which assesses pain severity and its impact on daily functions will be&#xD;
      administered to the patient in a language familiar to them, preoperatively, at 1, 4 and 6&#xD;
      months postoperatively.&#xD;
&#xD;
      The Musculoskeletal Tumour Society Score (MSTS) which evaluates the functional condition&#xD;
      (impairment) after completed tumour treatment will be estimated at the end of 6 months from&#xD;
      the date of surgery The painDETECT questionnaire (PD-Q) a quick, simple and reliable&#xD;
      screening tool to identify the likelihood of a neuropathic pain component in patients and&#xD;
      validated in various languages including Hindi and Marathi will be administered&#xD;
      preoperatively and at 1, 4 and 6 months after surgery.&#xD;
&#xD;
      Details of postoperative chemotherapy and radiation will also be obtained from patient's&#xD;
      notes and the electronic medical record. If the patient cannot follow up at the said&#xD;
      intervals, the pain scores would be obtained telephonically and the BPI and PD-Q forms in&#xD;
      prepaid envelopes would be given to them at discharge which they would have to duly fill in&#xD;
      and post them to the given address at the appropriate intervals if they cannot visit the pain&#xD;
      clinic. At the 6th month of follow up, they would be requested to visit the pain clinic for&#xD;
      an assessment of MSTS score and completing the BPI and PD-Q.&#xD;
&#xD;
      INCLUSION CRITERIA:-&#xD;
&#xD;
        -  Adult patients above 18 years of age, undergoing TKR&#xD;
&#xD;
        -  Literate: able to read and write in at least one of the following languages English,&#xD;
           Hindi and Marathi&#xD;
&#xD;
        -  Willing to fill forms and post them and/or answer questions on phone&#xD;
&#xD;
      EXCLUSION CRITERIA:-&#xD;
&#xD;
        -  Refusal of consent&#xD;
&#xD;
        -  Cognitively impaired&#xD;
&#xD;
        -  Revision TKRs (including cases with wound wash and nail spacer cementing)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION:- A Total Knee Replacement (TKR) or arthroplasty (TKA) is a complex procedure&#xD;
      that requires an Orthopedic Surgeon to make precise measurements and skillfully remove the&#xD;
      diseased portions of the bone, in order to shape the remaining bone to accommodate the knee&#xD;
      implant. Knee Replacement Surgery is most commonly performed in people with advanced&#xD;
      osteoarthritis and should be considered when conservative treatments have been exhausted.&#xD;
      Oncologic TKRs are different from the routine TKRs in a way that the former involves a wide&#xD;
      local resection of the bone and soft tissues, ranging from 10 to 20 cm, resection of muscles&#xD;
      like the head(s) of biceps femoris, the gastrocnemius muscle, the intermuscular septa, the&#xD;
      joint capsule, etc. to ensure negative margins along with the complete resection of the&#xD;
      tumour, followed by a reconstruction of almost the same length as that resected, to restore&#xD;
      function.&#xD;
&#xD;
      The most common indication for doing oncologic TKR is Osteogenic Sarcoma (OGS) of and around&#xD;
      the knee joint. The distal femur and proximal tibia are among the most common sites for&#xD;
      primary bone tumor. OGS is the most common bone cancer in the world in children and&#xD;
      adolescents, and the eighth-most common form of childhood cancer, accounting for 4% of all&#xD;
      childhood cancers worldwide. In India, the incidence varies from 4.7% to 11.6%, where this&#xD;
      malignancy is associated with significant morbidity and mortality. Additional treatment&#xD;
      involves chemotherapy which further delays the healing and recovery of the patient.&#xD;
&#xD;
      Surgery is a known risk factor for development of Chronic Post Surgical Pain(CPSP) which as&#xD;
      per the definition given by Macrae and Davies, is defined by&#xD;
&#xD;
        -  Pain developing after a surgical procedure.&#xD;
&#xD;
        -  Pain of at least 2 months' duration.&#xD;
&#xD;
        -  Other causes of pain excluded (e.g.- malignancy, infection, etc.).&#xD;
&#xD;
        -  Pain continuing from a pre-existing pain problem excluded.&#xD;
&#xD;
      CPSP is a well known risk factor in many surgeries like (but not exclusive of)-&#xD;
&#xD;
        -  Mastectomy (Incidence of chronic pain = 11-57%)&#xD;
&#xD;
        -  Amputation (30-85%)&#xD;
&#xD;
        -  Inguinal hernia(5-63%)&#xD;
&#xD;
        -  Cholecystectomy (3-50%)&#xD;
&#xD;
      CPSP develops after a surgical procedure or increases in intensity after the surgical&#xD;
      procedure. Literature on TKR surgeries indicated for osteoarthritis, report that although&#xD;
      many patients report a good outcome after their total knee replacement, at a time when&#xD;
      recovery should have been achieved, about 10-34% of patients undergoing TKR for&#xD;
      osteoarthritis report moderate to severe CPSP. In around 30% of patients with CPSP, the&#xD;
      origin of CPSP might be neuropathic. Neuropathic pain is more severe and adversely affects&#xD;
      the quality of life of patients. TKR on its own may cause neuropathic pain postoperatively&#xD;
      due to local nerve damage, often to the infrapatellar branch of the saphenous nerve or due to&#xD;
      local inflammation. Risk factors associated with the operation include increased duration of&#xD;
      surgery and tourniquet time, revision surgery, TKA versus unicompartmental arthroplasty and&#xD;
      intraoperative nerve damage. Oncologic TKRs are more extensive and include much morbid&#xD;
      excisions, and consequently may be presumed to have a similar if not a greater incidence of&#xD;
      CPSP. Some of the risk factors for CPSP include the following (but not exclusive of)-&#xD;
&#xD;
        -  Pain, moderate to severe, lasting more than 1 month&#xD;
&#xD;
        -  Repeat surgery&#xD;
&#xD;
        -  Younger age (adults)&#xD;
&#xD;
        -  Surgical approach with risk of nerve damage&#xD;
&#xD;
        -  Neurotoxic chemotherapy&#xD;
&#xD;
      Preoperative pain is consistently found to be a predictor for persistent postsurgical pain,&#xD;
      which might reflect an independent risk factor but could well be a manifestation of&#xD;
      predisposing factors.&#xD;
&#xD;
      Tata Memorial Hospital, a tertiary cancer institute is a 629 bedded hospital and conducts&#xD;
      approximately 6000 surgeries per year out of which approximately 100 TKRs are performed per&#xD;
      year. Analgesia peri-operatively is provided by an epidural infusion of a combination of&#xD;
      local anaesthetic and an opioid or intravenous opioids with non-steroidal anti-inflammatory&#xD;
      analgesics and paracetamol as appropriate. Postoperatively, if inserted, epidural analgesia&#xD;
      is continued for up to 3-4 days to help mobilization &amp; physiotherapy. In the absence of an&#xD;
      epidural, around the clock analgesics with or without an opioid administered by means of an&#xD;
      Intravenous Patient Controlled Analgesia (IVPCA) device is instituted. These patients are&#xD;
      visited by the acute pain service team to address pain issues for the first 3 postoperative&#xD;
      days or sometimes longer.&#xD;
&#xD;
      STUDY DESIGN:- Prospective and Observational study&#xD;
&#xD;
      METHODS and MATERIALS:- After Institutional Review Board approval, adult patients scheduled&#xD;
      for TKR surgeries will be enrolled into the study after obtaining their informed consent over&#xD;
      a 24 month period. However, interim analyses of all cases who have completed the 6 month&#xD;
      follow up as on 31st October, 2017 would be analyzed as part of the co- principle&#xD;
      investigator's thesis. All consenting patients will be assessed for their pain preoperatively&#xD;
      and for the first 3 post-operative days, and at 1, 4 and 6 months from the date of surgery.&#xD;
      Pain scores will be assessed using the Numerical Rating Scale during the 3 days after&#xD;
      surgery. Pain will be managed by the Acute Pain Service team as per the standard management&#xD;
      protocols.&#xD;
&#xD;
      The Brief pain inventory (BPI), (short form with translations, obtained with permission from&#xD;
      MD Anderson), which assesses the severity of pain and the impact of pain on daily functions&#xD;
      will be administered to the patient in the language familiar to them, preoperatively, at 1, 4&#xD;
      and 6 months postoperatively. The BPI is a useful instrument to assess the severity of pain&#xD;
      and impact of pain on daily functions in patients with pain from chronic diseases, conditions&#xD;
      such as cancer, osteoarthritis and low back pain, or with pain from acute conditions such as&#xD;
      postoperative pain. The short form comprises of nine questions related to the severity of&#xD;
      pain, impact of pain on daily function, location of pain, pain medications and amount of pain&#xD;
      relief in the past 24 hours or the past week. It has been widely used and validated in&#xD;
      several languages the world over.&#xD;
&#xD;
      The Musculoskeletal Tumour Society Score (MSTS) evaluates the functional condition&#xD;
      (impairment) after completed tumour treatment will be estimated at the end of 6 months from&#xD;
      the date of surgery. It is calculated on the basis of a standardized physical examination by&#xD;
      the physician. This clinical examination assesses six criteria and differs slightly between&#xD;
      the upper and lower limb. For the lower limb, the components are pain, function, emotional&#xD;
      acceptance of the treatment outcome, need for walking aids, walking and gait. For all&#xD;
      criteria, the estimate is made from bad to very good with parallel awarding of points (0 to&#xD;
      5). There is thus a numerical value for each of the six criteria. These six values are added&#xD;
      and divided by the maximum possible number of points (30). The percentage value is obtained&#xD;
      by multiplying the calculated point value by 100.&#xD;
&#xD;
      The painDETECT questionnaire (PD-Q) is a quick, simple and reliable screening tool to&#xD;
      identify the likelihood of a neuropathic pain component in patients with neuropathic pain.&#xD;
      This questionnaire had been prepared by professionals and validated in various languages&#xD;
      including Hindi and Marathi. Its sensitivity and specificity is higher than other screening&#xD;
      questionnaires for neuropathic pain, including the Douleur Neuropathique 4 (DN4), Leeds&#xD;
      Assessment of Neuropathic Symptoms and Signs (LANNS), and the Neuropathic Pain Questionnaire&#xD;
      (NPQ) (Freynhagen et al 2006). The PD-Q has been used to identify neuropathic pain in&#xD;
      patients with knee osteoarthritis (Ohtori et al 2012) and to identify sensory proﬁles in&#xD;
      patients with diabetic neuropathy and postherpetic neuralgia (Baron et al 2009).This&#xD;
      questionnaire will be administered tot he patients preoperatively , at 1, 4 and 6 months&#xD;
      after surgery.&#xD;
&#xD;
      Details of postoperative chemotherapy and radiation will also be obtained from patient's&#xD;
      notes and the electronic medical record. If the patient cannot follow up at the said&#xD;
      intervals, the pain scores would be obtained telephonically and the BPI and PD-Q forms in&#xD;
      prepaid envelopes would be given to them at discharge which they would have to duly fill in&#xD;
      and post them to the given address at the appropriate intervals if they cannot visit the pain&#xD;
      clinic. At the 6th month of follow up, they would be requested to visit the pain clinic for&#xD;
      an assessment of MSTS score and completing the BPI and PD-Q.&#xD;
&#xD;
      MEASUREMENTS:-&#xD;
&#xD;
        -  All demographic, preoperative, intraoperative and postoperative data would be collected&#xD;
           by the investigators.&#xD;
&#xD;
        -  Demographic data includes case no, age, sex, ASA (American Society of Anesthesiologists)&#xD;
           grade.&#xD;
&#xD;
        -  Preoperative variables include pain score, preoperative analgesics, duration of use, and&#xD;
           the dose.&#xD;
&#xD;
        -  Intraoperative variables include duration of surgery, tourniquet time, any nerve or&#xD;
           muscle resection and length of bone resected.&#xD;
&#xD;
        -  Postoperative variables include median average and worst pain score for the first 3&#xD;
           postoperative days , 1, 4 and 6 months after surgery.&#xD;
&#xD;
        -  Analgesics administered postoperatively, dose &amp; dosing intervals, impact on daily&#xD;
           functions as obtained from the BPI pre-operatively, 1, 4 and 6 months postoperatively.&#xD;
&#xD;
        -  The painDETECT score to identify the neuropathic component of pain if any,&#xD;
           preoperatively and at 1, 4 and 6 months after surgery.&#xD;
&#xD;
        -  The MSTS score calculated by the physician and obtained from the patient's record at the&#xD;
           6th month after surgery.&#xD;
&#xD;
      STATISTICAL ANALYSIS:- The above mentioned data will be presented as mean (sd), median&#xD;
      (range), and frequency (percentage). Categorical data will be analyzed using the Chi-square&#xD;
      test or Fisher Exact test (for binary data). Continuous variables will be analyzed using&#xD;
      paired t test or Wilcoxon signed rank test as per distribution of data. Repeated measure&#xD;
      ANOVA will be used for pain score analysis. Pearson correlation coefficients will be used for&#xD;
      association. p-value &lt;0.05 will be considered statistical significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2, 2017</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</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>pain severity in the immediate post-operative period following oncologic TKRs</measure>
    <time_frame>First 3 postoperative days</time_frame>
    <description>Pain scores as per the numerical rating scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the proportion of patients who continue to have pain at 4 and 6 months post surgery(CPSP)</measure>
    <time_frame>4 and 6 months after surgery</time_frame>
    <description>As assessed from the brief pain inventory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• To identify the type of pain (neuropathic component) persisting at 4 and 6 months after TKR</measure>
    <time_frame>4 and 6 months from surgery</time_frame>
    <description>Neuropathic component to be identified by using the pain Detect</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the pain on daily function</measure>
    <time_frame>4 and 6 months after surgery</time_frame>
    <description>Brief pain inventory and the MSTS score to assess the interference of pain with daily function and how it compares with MSTS at 6 month</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">139</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Pain, Chronic</condition>
  <condition>Osteogenic Sarcoma</condition>
  <condition>Knee Arthropathy</condition>
  <arm_group>
    <arm_group_label>Single group of patients</arm_group_label>
    <description>Non interventional study. Observational with questionnaires</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Non interventional study</intervention_name>
    <description>No intervention</description>
    <arm_group_label>Single group of patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients scheduled for total knee arthroplasty for osteogenic sarcoma&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients above 18 years of age, undergoing TKR&#xD;
&#xD;
          -  Literate: able to read and write in at least one of the following languages English,&#xD;
             Hindi and Marathi&#xD;
&#xD;
          -  Willing to fill forms and post them and/or answer questions on phone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal of consent&#xD;
&#xD;
          -  Cognitively impaired&#xD;
&#xD;
          -  Revision knee arthroplasty (including cases with wound wash and nail spacer cementing)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>APARNA S CHATTERJEE, MD,FCARCSI</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tata Memorial Centre</name>
      <address>
        <city>Mumbai</city>
        <state>Maharashtra</state>
        <zip>400012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <reference>
    <citation>Nguyen MP, Buckwalter JA, Miller BJ. Patterns of improvement following oncologic reconstructrion compared to total knee arthroplasty and revision knee arthroplasty. Iowa Orthop J. 2011;31:160-5.</citation>
    <PMID>22096436</PMID>
  </reference>
  <reference>
    <citation>Beswick AD, Wylde V, Gooberman-Hill R. Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials. BMJ Open. 2015 May 12;5(5):e007387. doi: 10.1136/bmjopen-2014-007387.</citation>
    <PMID>25967998</PMID>
  </reference>
  <reference>
    <citation>Haroutiunian S, Nikolajsen L, Finnerup NB, Jensen TS. The neuropathic component in persistent postsurgical pain: a systematic literature review. Pain. 2013 Jan;154(1):95-102. doi: 10.1016/j.pain.2012.09.010.</citation>
    <PMID>23273105</PMID>
  </reference>
  <reference>
    <citation>Ayers DC, Franklin PD, Ploutz-Snyder R, Boisvert CB. Total knee replacement outcome and coexisting physical and emotional illness. Clin Orthop Relat Res. 2005 Nov;440:157-61. doi: 10.1097/01.blo.0000185447.43622.93.</citation>
    <PMID>16239800</PMID>
  </reference>
  <reference>
    <citation>Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.</citation>
    <PMID>16698416</PMID>
  </reference>
  <reference>
    <citation>Tunn PU, Pomraenke D, Goerling U, Hohenberger P. Functional outcome after endoprosthetic limb-salvage therapy of primary bone tumours--a comparative analysis using the MSTS score, the TESS and the RNL index. Int Orthop. 2008 Oct;32(5):619-25. doi: 10.1007/s00264-007-0388-8. Epub 2007 Aug 15.</citation>
    <PMID>17701173</PMID>
  </reference>
  <reference>
    <citation>Mathieson S, Lin C. painDETECT questionnaire. J Physiother. 2013 Sep;59(3):211. doi: 10.1016/S1836-9553(13)70189-9. No abstract available.</citation>
    <PMID>23896340</PMID>
  </reference>
  <reference>
    <citation>Jain P, Padole D, Bakshi S. Prevalence of acute neuropathic pain after cancer surgery: A prospective study. Indian J Anaesth. 2014 Jan;58(1):36-42. doi: 10.4103/0019-5049.126788.</citation>
    <PMID>24700897</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>October 7, 2020</last_update_submitted>
  <last_update_submitted_qc>October 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tata Memorial Centre</investigator_affiliation>
    <investigator_full_name>Dr Aparna Chatterjee</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>pain, acute, chronic, knee arthroplasty</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteosarcoma</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03032679
org study id: 1780
nct id: NCT03032679
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
After Institutional Review Board approval, adult patients scheduled for total knee
      arthroplasty (TKA) will be enrolled into the study after obtaining informed consent over a 24
      month period. Interim analyses of cases who have completed the 6 month follow up as on 31st
      October, 2017 will be analyzed as part of the co- principle investigator's thesis. All
      consenting patients will be assessed for pain preoperatively, the first 3 post-operative
      days, at 1, 4 and 6 months from the date of surgery. Pain scores will be assessed using the
      Numerical Rating Scale during the 3 postoperative days. Pain will be managed by the Acute
      Pain Service team as per standard protocols.

      The Brief pain inventory (BPI) (short form with translations, obtained with permission from
      MD Anderson), which assesses pain severity and its impact on daily functions will be
      administered to the patient in a language familiar to them, preoperatively, at 1, 4 and 6
      months postoperatively.

      The Musculoskeletal Tumour Society Score (MSTS) which evaluates the functional condition
      (impairment) after completed tumour treatment will be estimated at the end of 6 months from
      the date of surgery The painDETECT questionnaire (PD-Q) a quick, simple and reliable
      screening tool to identify the likelihood of a neuropathic pain component in patients and
      validated in various languages including Hindi and Marathi will be administered
      preoperatively and at 1, 4 and 6 months after surgery.

      Details of postoperative chemotherapy and radiation will also be obtained from patient's
      notes and the electronic medical record. If the patient cannot follow up at the said
      intervals, the pain scores would be obtained telephonically and the BPI and PD-Q forms in
      prepaid envelopes would be given to them at discharge which they would have to duly fill in
      and post them to the given address at the appropriate intervals if they cannot visit the pain
      clinic. At the 6th month of follow up, they would be requested to visit the pain clinic for
      an assessment of MSTS score and completing the BPI and PD-Q.

      INCLUSION CRITERIA:-

        -  Adult patients above 18 years of age, undergoing TKR

        -  Literate: able to read and write in at least one of the following languages English,
           Hindi and Marathi

        -  Willing to fill forms and post them and/or answer questions on phone

      EXCLUSION CRITERIA:-

        -  Refusal of consent

        -  Cognitively impaired

        -  Revision TKRs (including cases with wound wash and nail spacer cementing)
INTRODUCTION:- A Total Knee Replacement (TKR) or arthroplasty (TKA) is a complex procedure
      that requires an Orthopedic Surgeon to make precise measurements and skillfully remove the
      diseased portions of the bone, in order to shape the remaining bone to accommodate the knee
      implant. Knee Replacement Surgery is most commonly performed in people with advanced
      osteoarthritis and should be considered when conservative treatments have been exhausted.
      Oncologic TKRs are different from the routine TKRs in a way that the former involves a wide
      local resection of the bone and soft tissues, ranging from 10 to 20 cm, resection of muscles
      like the head(s) of biceps femoris, the gastrocnemius muscle, the intermuscular septa, the
      joint capsule, etc. to ensure negative margins along with the complete resection of the
      tumour, followed by a reconstruction of almost the same length as that resected, to restore
      function.

      The most common indication for doing oncologic TKR is Osteogenic Sarcoma (OGS) of and around
      the knee joint. The distal femur and proximal tibia are among the most common sites for
      primary bone tumor. OGS is the most common bone cancer in the world in children and
      adolescents, and the eighth-most common form of childhood cancer, accounting for 4% of all
      childhood cancers worldwide. In India, the incidence varies from 4.7% to 11.6%, where this
      malignancy is associated with significant morbidity and mortality. Additional treatment
      involves chemotherapy which further delays the healing and recovery of the patient.

      Surgery is a known risk factor for development of Chronic Post Surgical Pain(CPSP) which as
      per the definition given by Macrae and Davies, is defined by

        -  Pain developing after a surgical procedure.

        -  Pain of at least 2 months' duration.

        -  Other causes of pain excluded (e.g.- malignancy, infection, etc.).

        -  Pain continuing from a pre-existing pain problem excluded.

      CPSP is a well known risk factor in many surgeries like (but not exclusive of)-

        -  Mastectomy (Incidence of chronic pain = 11-57%)

        -  Amputation (30-85%)

        -  Inguinal hernia(5-63%)

        -  Cholecystectomy (3-50%)

      CPSP develops after a surgical procedure or increases in intensity after the surgical
      procedure. Literature on TKR surgeries indicated for osteoarthritis, report that although
      many patients report a good outcome after their total knee replacement, at a time when
      recovery should have been achieved, about 10-34% of patients undergoing TKR for
      osteoarthritis report moderate to severe CPSP. In around 30% of patients with CPSP, the
      origin of CPSP might be neuropathic. Neuropathic pain is more severe and adversely affects
      the quality of life of patients. TKR on its own may cause neuropathic pain postoperatively
      due to local nerve damage, often to the infrapatellar branch of the saphenous nerve or due to
      local inflammation. Risk factors associated with the operation include increased duration of
      surgery and tourniquet time, revision surgery, TKA versus unicompartmental arthroplasty and
      intraoperative nerve damage. Oncologic TKRs are more extensive and include much morbid
      excisions, and consequently may be presumed to have a similar if not a greater incidence of
      CPSP. Some of the risk factors for CPSP include the following (but not exclusive of)-

        -  Pain, moderate to severe, lasting more than 1 month

        -  Repeat surgery

        -  Younger age (adults)

        -  Surgical approach with risk of nerve damage

        -  Neurotoxic chemotherapy

      Preoperative pain is consistently found to be a predictor for persistent postsurgical pain,
      which might reflect an independent risk factor but could well be a manifestation of
      predisposing factors.

      Tata Memorial Hospital, a tertiary cancer institute is a 629 bedded hospital and conducts
      approximately 6000 surgeries per year out of which approximately 100 TKRs are performed per
      year. Analgesia peri-operatively is provided by an epidural infusion of a combination of
      local anaesthetic and an opioid or intravenous opioids with non-steroidal anti-inflammatory
      analgesics and paracetamol as appropriate. Postoperatively, if inserted, epidural analgesia
      is continued for up to 3-4 days to help mobilization & physiotherapy. In the absence of an
      epidural, around the clock analgesics with or without an opioid administered by means of an
      Intravenous Patient Controlled Analgesia (IVPCA) device is instituted. These patients are
      visited by the acute pain service team to address pain issues for the first 3 postoperative
      days or sometimes longer.

      STUDY DESIGN:- Prospective and Observational study

      METHODS and MATERIALS:- After Institutional Review Board approval, adult patients scheduled
      for TKR surgeries will be enrolled into the study after obtaining their informed consent over
      a 24 month period. However, interim analyses of all cases who have completed the 6 month
      follow up as on 31st October, 2017 would be analyzed as part of the co- principle
      investigator's thesis. All consenting patients will be assessed for their pain preoperatively
      and for the first 3 post-operative days, and at 1, 4 and 6 months from the date of surgery.
      Pain scores will be assessed using the Numerical Rating Scale during the 3 days after
      surgery. Pain will be managed by the Acute Pain Service team as per the standard management
      protocols.

      The Brief pain inventory (BPI), (short form with translations, obtained with permission from
      MD Anderson), which assesses the severity of pain and the impact of pain on daily functions
      will be administered to the patient in the language familiar to them, preoperatively, at 1, 4
      and 6 months postoperatively. The BPI is a useful instrument to assess the severity of pain
      and impact of pain on daily functions in patients with pain from chronic diseases, conditions
      such as cancer, osteoarthritis and low back pain, or with pain from acute conditions such as
      postoperative pain. The short form comprises of nine questions related to the severity of
      pain, impact of pain on daily function, location of pain, pain medications and amount of pain
      relief in the past 24 hours or the past week. It has been widely used and validated in
      several languages the world over.

      The Musculoskeletal Tumour Society Score (MSTS) evaluates the functional condition
      (impairment) after completed tumour treatment will be estimated at the end of 6 months from
      the date of surgery. It is calculated on the basis of a standardized physical examination by
      the physician. This clinical examination assesses six criteria and differs slightly between
      the upper and lower limb. For the lower limb, the components are pain, function, emotional
      acceptance of the treatment outcome, need for walking aids, walking and gait. For all
      criteria, the estimate is made from bad to very good with parallel awarding of points (0 to
      5). There is thus a numerical value for each of the six criteria. These six values are added
      and divided by the maximum possible number of points (30). The percentage value is obtained
      by multiplying the calculated point value by 100.

      The painDETECT questionnaire (PD-Q) is a quick, simple and reliable screening tool to
      identify the likelihood of a neuropathic pain component in patients with neuropathic pain.
      This questionnaire had been prepared by professionals and validated in various languages
      including Hindi and Marathi. Its sensitivity and specificity is higher than other screening
      questionnaires for neuropathic pain, including the Douleur Neuropathique 4 (DN4), Leeds
      Assessment of Neuropathic Symptoms and Signs (LANNS), and the Neuropathic Pain Questionnaire
      (NPQ) (Freynhagen et al 2006). The PD-Q has been used to identify neuropathic pain in
      patients with knee osteoarthritis (Ohtori et al 2012) and to identify sensory proﬁles in
      patients with diabetic neuropathy and postherpetic neuralgia (Baron et al 2009).This
      questionnaire will be administered tot he patients preoperatively , at 1, 4 and 6 months
      after surgery.

      Details of postoperative chemotherapy and radiation will also be obtained from patient's
      notes and the electronic medical record. If the patient cannot follow up at the said
      intervals, the pain scores would be obtained telephonically and the BPI and PD-Q forms in
      prepaid envelopes would be given to them at discharge which they would have to duly fill in
      and post them to the given address at the appropriate intervals if they cannot visit the pain
      clinic. At the 6th month of follow up, they would be requested to visit the pain clinic for
      an assessment of MSTS score and completing the BPI and PD-Q.

      MEASUREMENTS:-

        -  All demographic, preoperative, intraoperative and postoperative data would be collected
           by the investigators.

        -  Demographic data includes case no, age, sex, ASA (American Society of Anesthesiologists)
           grade.

        -  Preoperative variables include pain score, preoperative analgesics, duration of use, and
           the dose.

        -  Intraoperative variables include duration of surgery, tourniquet time, any nerve or
           muscle resection and length of bone resected.

        -  Postoperative variables include median average and worst pain score for the first 3
           postoperative days , 1, 4 and 6 months after surgery.

        -  Analgesics administered postoperatively, dose & dosing intervals, impact on daily
           functions as obtained from the BPI pre-operatively, 1, 4 and 6 months postoperatively.

        -  The painDETECT score to identify the neuropathic component of pain if any,
           preoperatively and at 1, 4 and 6 months after surgery.

        -  The MSTS score calculated by the physician and obtained from the patient's record at the
           6th month after surgery.

      STATISTICAL ANALYSIS:- The above mentioned data will be presented as mean (sd), median
      (range), and frequency (percentage). Categorical data will be analyzed using the Chi-square
      test or Fisher Exact test (for binary data). Continuous variables will be analyzed using
      paired t test or Wilcoxon signed rank test as per distribution of data. Repeated measure
      ANOVA will be used for pain score analysis. Pearson correlation coefficients will be used for
      association. p-value <0.05 will be considered statistical significant.
observational model: Cohort
time perspective: Prospective
measure: pain severity in the immediate post-operative period following oncologic TKRs
time frame: First 3 postoperative days
description: Pain scores as per the numerical rating scale
measure: the proportion of patients who continue to have pain at 4 and 6 months post surgery(CPSP)
time frame: 4 and 6 months after surgery
description: As assessed from the brief pain inventory
measure: • To identify the type of pain (neuropathic component) persisting at 4 and 6 months after TKR
time frame: 4 and 6 months from surgery
description: Neuropathic component to be identified by using the pain Detect
measure: Impact of the pain on daily function
time frame: 4 and 6 months after surgery
description: Brief pain inventory and the MSTS score to assess the interference of pain with daily function and how it compares with MSTS at 6 month
arm group label: Single group of patients
description: Non interventional study. Observational with questionnaires
intervention type: Other
intervention name: Non interventional study
description: No intervention
arm group label: Single group of patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: APARNA S CHATTERJEE, MD,FCARCSI
role: Principal Investigator
affiliation: Professor
facility: 
country: India
citation: Nguyen MP, Buckwalter JA, Miller BJ. Patterns of improvement following oncologic reconstructrion compared to total knee arthroplasty and revision knee arthroplasty. Iowa Orthop J. 2011;31:160-5.
PMID: 22096436
citation: Beswick AD, Wylde V, Gooberman-Hill R. Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials. BMJ Open. 2015 May 12;5(5):e007387. doi: 10.1136/bmjopen-2014-007387.
PMID: 25967998
citation: Haroutiunian S, Nikolajsen L, Finnerup NB, Jensen TS. The neuropathic component in persistent postsurgical pain: a systematic literature review. Pain. 2013 Jan;154(1):95-102. doi: 10.1016/j.pain.2012.09.010.
PMID: 23273105
citation: Ayers DC, Franklin PD, Ploutz-Snyder R, Boisvert CB. Total knee replacement outcome and coexisting physical and emotional illness. Clin Orthop Relat Res. 2005 Nov;440:157-61. doi: 10.1097/01.blo.0000185447.43622.93.
PMID: 16239800
citation: Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.
PMID: 16698416
citation: Tunn PU, Pomraenke D, Goerling U, Hohenberger P. Functional outcome after endoprosthetic limb-salvage therapy of primary bone tumours--a comparative analysis using the MSTS score, the TESS and the RNL index. Int Orthop. 2008 Oct;32(5):619-25. doi: 10.1007/s00264-007-0388-8. Epub 2007 Aug 15.
PMID: 17701173
citation: Mathieson S, Lin C. painDETECT questionnaire. J Physiother. 2013 Sep;59(3):211. doi: 10.1016/S1836-9553(13)70189-9. No abstract available.
PMID: 23896340
citation: Jain P, Padole D, Bakshi S. Prevalence of acute neuropathic pain after cancer surgery: A prospective study. Indian J Anaesth. 2014 Jan;58(1):36-42. doi: 10.4103/0019-5049.126788.
PMID: 24700897
responsible party type: Principal Investigator
investigator affiliation: Tata Memorial Centre
investigator full name: Dr Aparna Chatterjee
investigator title: Professor
mesh term: Osteosarcoma
mesh term: Chronic Pain
mesh term: Pain, Postoperative
sharing ipd: No