Clinical trial NCT04949646: Intraoperative Neuromonitoring of Pelvic Autonomous Nerve Plexus During Total Mesorectal Excision
Official title: Intraoperative Neuromonitoring of Pelvic Autonomous Nerve Plexus During Total Mesorectal Excision
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Neoplasms
Keywords: intraoperative
neuromonitoring
pelvic
autonomous
total
mesorectal
excision
Lead sponsor: Larissa University Hospital
Sponsor class: OTHER
Collaborators: name: General Hospital of Larissa
name: University of Thessaly
First posted: 2021-07-02
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will employ a prospective, parallel randomized-controlled design
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the quality of life of the patient at 3 months postoperatively, based on the SF-36 questionnaire
timeFrame: Preoperatively, 3 months postoperatively
Secondary outcomes:
measure: Operative time
timeFrame: Intraoperative period
measure: Intraoperative bleeding
timeFrame: Intraoperative period
measure: Postoperative discharge time
timeFrame: Maximum time frame 15 days postoperatively
measure: Postoperative complications
timeFrame: 1 month postoperatively
measure: Negative resection margin
timeFrame: 1 month postoperatively
measure: Local recurrence
timeFrame: 1 year postoperatively
measure: Bladder capacity
timeFrame: Preoperatively and 2 months postoperatively
measure: Bladder compliance
timeFrame: Preoperatively and 2 months postoperatively
measure: Detrusor pressure at maximum flow
timeFrame: Preoperatively and 2 months postoperatively
measure: Maximum urinary flow rate
timeFrame: Preoperatively and 2 months postoperatively
measure: Voiding volume
timeFrame: Preoperatively and 2 months postoperatively
measure: Post-void residual
timeFrame: Preoperatively and 2 months postoperatively
measure: Anal canal resting phase pressure
timeFrame: Preoperatively and 2 months postoperatively
measure: Sphincter zone length
timeFrame: Preoperatively and 2 months postoperatively
measure: Short squeeze test
timeFrame: Preoperatively and 2 months postoperatively
measure: Long squeeze test
timeFrame: Preoperatively and 2 months postoperatively
measure: Cough test
timeFrame: Preoperatively and 2 months postoperatively
measure: Push test
timeFrame: Preoperatively and 2 months postoperatively
measure: RAIR test
timeFrame: Preoperatively and 2 months postoperatively
measure: Difference in the quality of life of the patient, based on the SF-36 questionnaire
timeFrame: Preoperatively, 6, 12, 24 months postoperatively
measure: Difference in the erectile function of the patient, based on the IIEF questionnaire
timeFrame: Preoperatively, 3, 6, 12, 24 months postoperatively
measure: Difference in the sexual function of the patient, based on the FSFI questionnaire
timeFrame: Preoperatively, 3, 6, 12, 24 months postoperatively
measure: Difference in the prostate symptoms of the patient, based on the IPSS questionnaire
timeFrame: Preoperatively, 3, 6, 12, 24 months postoperatively
measure: Difference in the low anterior syndrome symptoms of the patient, based on the LARS questionnaire
timeFrame: Preoperatively, 3, 6, 12, 24 months postoperatively
Other outcomes:
Locations:
city: Larissa
country: Greece
facility: University Hospital of Larissa
Study officials:
affiliation: Department of Surgery, University Hospital of Larissa
name: Konstantinos Tepetes, Prof
role: STUDY_DIRECTOR
affiliation: Department of Surgery, University Hospital of Larissa
name: Konstantinos Perivoliotis, MD
role: PRINCIPAL_INVESTIGATOR
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