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Intraoperative Neuromonitoring of Pelvic Autonomous Nerve Plexus During Total Mesorectal Excision

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ClinicalTrials.gov Identifier: NCT04949646
Recruitment Status : Recruiting
First Posted : July 2, 2021
Last Update Posted : March 13, 2024
Sponsor:
Collaborators:
General Hospital of Larissa
University of Thessaly
Information provided by (Responsible Party):
Perivoliotis Konstantinos, Larissa University Hospital

Tracking Information
First Submitted Date  ICMJE June 22, 2021
First Posted Date  ICMJE July 2, 2021
Last Update Posted Date March 13, 2024
Actual Study Start Date  ICMJE September 19, 2021
Estimated Primary Completion Date September 19, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2021)
Change in the quality of life of the patient at 3 months postoperatively, based on the SF-36 questionnaire [ Time Frame: Preoperatively, 3 months postoperatively ]
Change in the quality of life of the patient, at 3 months postoperatively, compared to the respective preoperative measurements, based on the Short Form 36 (SF-36) questionnaire SF-36: Short Form Survey Minimum Value: 0 Maximum Value: 100 Higher scores indicate a better outcome
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2021)
  • Operative time [ Time Frame: Intraoperative period ]
    The total operative time will be recorded. Measurement unit: minutes
  • Intraoperative bleeding [ Time Frame: Intraoperative period ]
    The total intraoperative blood loss volume will be recorded. Measurement unit: mL
  • Postoperative discharge time [ Time Frame: Maximum time frame 15 days postoperatively ]
    Postoperative time that the patient can be safely discharged. Measurement unit: hours. The patient will be discharged, when it is ensured that is medically safe to be released. In particular, as the exit time of the patient, will be regarded the time that the patient will fulfil the Clinical Discharge Criteria. More specifically, the patient should meet the following : steady vital signs, be oriented, without nausea or vomiting, mobilized with a steady gait, without a significant bleeding
  • Postoperative complications [ Time Frame: 1 month postoperatively ]
    Occurrence of postoperative complications (based on Clavien-Dindo classification). If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
  • Negative resection margin [ Time Frame: 1 month postoperatively ]
    Occurrence of negative resection margin. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
  • Local recurrence [ Time Frame: 1 year postoperatively ]
    Occurrence of local recurrence. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
  • Bladder capacity [ Time Frame: Preoperatively and 2 months postoperatively ]
    Urodynamic assessment. Evaluation of bladder capacity. Measurement unit: ml
  • Bladder compliance [ Time Frame: Preoperatively and 2 months postoperatively ]
    Urodynamic assessment. Evaluation of bladder compliance. Measurement unit: ml/cm H2O
  • Detrusor pressure at maximum flow [ Time Frame: Preoperatively and 2 months postoperatively ]
    Urodynamic assessment. Evaluation of detrusor pressure at maximum flow. Measurement unit: cm H2O
  • Maximum urinary flow rate [ Time Frame: Preoperatively and 2 months postoperatively ]
    Urodynamic assessment. Evaluation of maximum urinary flow rate. Measurement unit: ml/s
  • Voiding volume [ Time Frame: Preoperatively and 2 months postoperatively ]
    Urodynamic assessment. Evaluation of voiding volume. Measurement unit: ml
  • Post-void residual [ Time Frame: Preoperatively and 2 months postoperatively ]
    Urodynamic assessment. Evaluation of post-void residual. Measurement unit: ml
  • Anal canal resting phase pressure [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of anal canal resting phase pressure. Measurement unit: mmHg
  • Sphincter zone length [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of sphincter zone length. Measurement unit: cm
  • Short squeeze test [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of short squeeze (5sec) pressure. Measurement unit: mmHg
  • Long squeeze test [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of long squeeze (30sec) pressure. Measurement unit: mmHg
  • Cough test [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of cough test (0 and 50 ml). If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
  • Push test [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of push test (0 and 50 ml). If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
  • RAIR test [ Time Frame: Preoperatively and 2 months postoperatively ]
    High-resolution Anorectal Manometry assessment. Evaluation of rectoanal inhibitory reflex (RAIR) test (20 and 50 ml). If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
  • Difference in the quality of life of the patient, based on the SF-36 questionnaire [ Time Frame: Preoperatively, 6, 12, 24 months postoperatively ]
    Difference in the quality of life of the patient, at 6, 12, 24 months postoperatively, compared to the respective preoperative measurements, based on the Short Form 36 (SF-36) questionnaire SF-36: Short Form Survey Minimum Value: 0 Maximum Value: 100 Higher scores indicate a better outcome
  • Difference in the erectile function of the patient, based on the IIEF questionnaire [ Time Frame: Preoperatively, 3, 6, 12, 24 months postoperatively ]
    Difference in the erectile function of the patient, at 3, 6, 12, 24 months postoperatively, compared to the respective preoperative measurements, based on the International Index of Erectile Function (IIEF) questionnaire IIEF: International Index of Erectile Function Minimum Value: 0 Maximum Value: 5 Higher scores indicate a better outcome
  • Difference in the sexual function of the patient, based on the FSFI questionnaire [ Time Frame: Preoperatively, 3, 6, 12, 24 months postoperatively ]
    Difference in the sexual function of the patient, at 3, 6, 12, 24 months postoperatively, compared to the respective preoperative measurements, based on the Female Sexual Function Index (FSFI) questionnaire FSFI: Female Sexual Function Index Minimum Value: 2 Maximum Value: 36 Higher scores indicate a better outcome
  • Difference in the prostate symptoms of the patient, based on the IPSS questionnaire [ Time Frame: Preoperatively, 3, 6, 12, 24 months postoperatively ]
    Difference in the prostate symptoms of the patient, at 3, 6, 12, 24 months postoperatively, compared to the respective preoperative measurements, based on the International Prostate Symptom Score (IPSS) questionnaire IPSS: International Prostate Symptom Score Minimum Value: 0 Maximum Value: 35 Higher scores indicate a worse outcome
  • Difference in the low anterior syndrome symptoms of the patient, based on the LARS questionnaire [ Time Frame: Preoperatively, 3, 6, 12, 24 months postoperatively ]
    Difference in the low anterior syndrome symptoms of the patient, at 3, 6, 12, 24 months postoperatively, compared to the respective preoperative measurements, based on the Low Anterior Resection Syndrome (LARS) questionnaire LARS: Low Anterior Resection Syndrome Minimum Value: 0 Maximum Value: 42 Higher scores indicate a worse outcome
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intraoperative Neuromonitoring of Pelvic Autonomous Nerve Plexus During Total Mesorectal Excision
Official Title  ICMJE Intraoperative Neuromonitoring of Pelvic Autonomous Nerve Plexus During Total Mesorectal Excision
Brief Summary The purpose of this research protocol is the evaluation of the improvement of the anorectal and urogenital urinary function, alongside the postoperative quality of life after the application of pIONM in patients submitted to TME for rectal cancer.
Detailed Description

The introduction of Total Mesorectal Excision (TME) resulted to the improvement of the overall survival and local recurrence rates of rectal cancer patients. However, the associated urogenital and anorectal functional deficit has a significant effect on the postoperative quality of life of the patient. More specifically, the postoperative rates of urogenital and sexual dysfunction that have been reported in the various series, are estimated at the levels of 70% and 90%, respectively. Additionally, TME is associated with the development of the low anterior syndrome (LARS). LARS is characterized by the onset of fecal incontinence, due to injury in the autonomic nerve plexuses that innervate the internal anal sphincter (IAS); who in turn is responsible for the 52-85% anal resting tone. According to a recent study, 38.8% and 33.7% of patients with normal preoperative urogenital function, developed postoperative stool and urine incontinence, respectively.

It becomes apparent that the incidence rates of these complications vary between the various series, mainly due to their small sample size, the lack of comparative data, the short follow up period, the use of non-validated tools and their retrospective design. Several predictive factors of these adverse events have been suggested in the literature, including old age, tumors located less than 12 cm from the anal verge, preoperative radiotherapy and injury to the pelvic autonomous nerves.

The clinical and functional anatomy of the pelvis are quite complex. The inferior hypogastric plexus is formed by the parasympathetic pelvic nerves, deriving from the I2-I4 and the sympathetic hypogastric nerve. It is a neural anatomic structure that carries organ-specific nerve fibers. Visual identification of the plexus is quite difficult, for various reasons, including the complexity of the nerve distribution, the narrow pelvis, the voluminous mesorectum, obesity, previous pelvic operations, neoadjuvant radiotherapy, locally advanced tumors, intraoperative bleeding and the extensive use of diathermy. According to the current literature, identification of the autonomous pelvic plexus is achievable in 72% of cases, whereas partial localization is possible only in 10.7% of patients.

Theoretically, intraoperative neuromonitoring of the pelvic autonomous nerves (pIONM), could quantify intraoperative nerve injuries, while in parallel, contribute to the improvement of the patients' postoperative quality of life. Several pIONM techniques have been described, including intra-urethral and intra-vesical pressure measurements. However, it was found that intermittent neuromonitoring objectifies the macroscopic integrity assessment of the sacral plexus. Recently, a promising technique, based on the simultaneous electromyography of the IAS and bladder manometry was developed, with encouraging results. During pIONM, the surgeon delivers electric stimuli to the autonomic nerve structures through a hand-held stimulator. At the same time, electromyogram changes of the IAS and the external anal sphincter (EAS), alongside intravesical pressure gradients are assessed.

Intraoperative neuromonitoring has been evaluated in several experimental studies. In a recent study, intraoperative simulation of the inferior hypogastric plexus with a bipolar stimulator resulted to the appearance of a measurable and repeatable electromyographic signal from the IAS.

Simultaneous signal processing from the IAS and urinary bladder, improves the, overall, diagnostic accuracy of these techniques. Stabilization of the electrodes outside the surgical field, has been, also, suggested by some researchers. Additionally, experimental studies evaluated the role of pIONM in the minimal invasive TME.

Moreover, the effectiveness of this technique has been a research subject in multiple clinical trials. In another study, where 85 patients underwent TME, after logistic regression, no use of pIONM and neoadjuvant radiotherapy, were identified as independent prognostic factors of postoperative urogenital deficit. Furthermore, the use of pIONM, was associated with a 100% sensitivity and a 96% specificity for the postoperative development of urogenital and anorectal functional complications.

The application of pIONM has been also suggested in the laparoscopic and robotic TME, using specially designed stimulators. In another trial, preservation of the plexus was achieved in 51.7% of patients submitted to a laparoscopic low anterior resection for rectal cancer. During one year follow-up, patients receiving pIONM, displayed a superiority in terms of postoperative urogenital function, as assessed by the IIEF, IPSS and FSFI questionnaires.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study will employ a prospective, parallel randomized-controlled design
Masking: Single (Participant)
Masking Description:
The patient will be blinded regarding the allocation group. Blinding will not exist at the level of the surgeon, the anaesthesiologist, and the investigator responsible for the data recording
Primary Purpose: Treatment
Condition  ICMJE Rectal Neoplasms
Intervention  ICMJE Other: Pelvic Intraoperative Neuromonitoring
Pelvic Intraoperative Neuromonitoring (pIONM) allows mapping of the pelvic autonomous plexus during total mesorectal excision (TME).
Study Arms  ICMJE
  • Experimental: pIONM

    In the experimental group pIONM will be performed intraoperatively. For the implementation of pIONM, a special device, that allows simultaneous monitoring of sphincter signals and bladder manometry, will be introduced. This device will employ the placement of a bipolar electrode in the internal and external anal sphincter. Moreover, another electrode will be placed on the surrounding tissues. For bladder manometry, the catheter will be connected to the pressure sensor, and subsequently to the pIONM monitor. Intraoperatively, depending on the approach (open or laparoscopic), the respective bipolar stimulator will be used.

    Prior to the initiation of pIONM, urinary bladder will be drained and filled with 200 ml R/L. The pIONM parameters will be the following: 1-25 milliampere current, 30 Hz frequency and 200 μs monophasic pulses.

    Intervention: Other: Pelvic Intraoperative Neuromonitoring
  • No Intervention: Control
    In the control group pIONM will not be performed intraoperatively
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 30, 2021)
44
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 19, 2027
Estimated Primary Completion Date September 19, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed rectal cancer
  • Surgical resection with TME
  • <90 years old
  • Signed informed consent

Exclusion Criteria:

  • Emergency operation
  • Presence of pacemaker
  • Partial mesorectal excision
  • Sepsis or systematic infection
  • Physical or mental impairment
  • Pregnancy or nursing
  • Insufficient preoperative data for the urogenital/ anorectal function
  • Lack of compliance with the research process
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Konstantinos Tepetes, Prof 00302413502804 tepetesk@gmail.com
Contact: Konstantinos Perivoliotis, MD 00302413501000 kperi19@gmail.com
Listed Location Countries  ICMJE Greece
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04949646
Other Study ID Numbers  ICMJE PelIONM
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No plan to share individual patient data
Current Responsible Party Perivoliotis Konstantinos, Larissa University Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Larissa University Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • General Hospital of Larissa
  • University of Thessaly
Investigators  ICMJE
Study Director: Konstantinos Tepetes, Prof Department of Surgery, University Hospital of Larissa
Principal Investigator: Konstantinos Perivoliotis, MD Department of Surgery, University Hospital of Larissa
PRS Account Larissa University Hospital
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP