Pelvic Intraoperative Neuromonitoring Prevents Dysfunction in Patients With Rectal Cancer: Results From a Multicenter, Randomized, Controlled Clinical Trial of a NEUROmonitoring System (NEUROS).

OBJECTIVE: This NEUROmonitoring System (NEUROS) trial assessed whether pelvic intraoperative neuromonitoring (pIONM) could improve urogenital and ano-(neo-)rectal functional outcomes in patients who underwent total mesorectal excisions (TMEs) for rectal cancer. BACKGROUND: High-level evidence from clinical trials is required to clarify the benefits of pIONM. METHODS: NEUROS was a 2-arm, randomized, controlled, multicenter clinical trial that included 189 patients with rectal cancer who underwent TMEs at 8 centers, from February 2013 to January 2017. TMEs were performed with pIONM (n=90) or without it (control, n=99). The groups were stratified according to neoadjuvant chemoradiotherapy and sex, with blocks of variable length. Data were analyzed according to a modified intention-to-treat protocol. The primary endpoint was a urinary function at 12 months after surgery, assessed with the International Prostate Symptom Score, a patient-reported outcome measure. Deterioration was defined as an increase of at least 5 points from the preoperative score. Secondary endpoints were sexual and anorectal functional outcomes, safety, and TME quality. RESULTS: The intention-to-treat analysis included 171 patients. Marked urinary deterioration occurred in 22/171 (13%) patients, with significantly different incidence between groups (pIONM: n=6/82, 8%; control: n=16/89, 19%; 95% confidence interval, 12.4-94.4; P =0.0382). pIONM was associated with better sexual and ano-(neo)rectal function. At least 1 serious adverse event occurred in 36/88 (41%) in the pIONM group and 53/99 (54%) in the control group, none associated with the study treatment. The groups had similar TME quality, surgery times, intraoperative complication incidence, and postoperative mortality. CONCLUSION: pIONM is safe and has the potential to improve functional outcomes in rectal cancer patients undergoing TME.

Fecal incontinence after total mesorectal excision for rectal cancer-impact of potential risk factors and pelvic intraoperative neuromonitoring.

BACKGROUND: Fecal incontinence frequently occurs after total mesorectal excision for rectal cancer. This prospective study analyzed predictive factors and the impact of pelvic intraoperative neuromonitoring at different follow-up intervals. METHODS: Fifty-two patients were included undergoing total mesorectal excision for rectal cancer, and 29 under control of pelvic intraoperative neuromonitoring. Fecal incontinence was assessed using the Wexner Score at 3 and 6 months after stoma closure (follow-ups 1 and 2) as well as 1 and 2 years after surgery (follow-ups 3 and 4). Risk factors were identified by means of logistic regression. RESULTS: New onset of fecal incontinence was significantly lower in the neuromonitoring group at each follow-up (follow-up 1: 2 of 29 patients (7%) vs. 8 of 23 (35%), (p = 0.014); follow-up 2: 3 of 29 (10%) vs. 9 of 23 (39%), (p = 0.017); follow-up 3: 5 of 29 (17%) vs. 11 of 23 (48%), p = 0.019; follow-up 4: 6 of 28 (21%) vs. 11 of 22 (50%), p = 0.035). Non-performance of neuromonitoring was found to be an independent predictor for fecal incontinence throughout the survey. Neoadjuvant chemoradiotherapy was an independent predictor in the further course 1 and 2 years after surgery. CONCLUSIONS: Performance of pelvic intraoperative neuromonitoring is associated with significantly lower rates of fecal incontinence. Neoadjuvant chemoradiotherapy was found to have negative late effects. This became evident 1 year after surgery.

Management of cecal diverticulitis diagnosed by computed tomography scan.

PURPOSE: Cecal diverticulitis is a rare entity causing right iliac fossa pain. Its symptoms may mimic acute appendicitis. Therefore, the majority of these patients undergo unnecessary surgery for suspected diagnosis of appendicitis. METHODS: We report a case series of solitary cecal diverticulitis, right-sided colonic diverticulitis, and perforated cecal diverticulitis diagnosed by computed tomography scan. RESULTS: The first two cases were successfully managed conservatively with intravenous antibiotics, rehydration, and temporary bowel rest. The third case developed a retroperitoneal abscess, which was initially drained under computed tomography guidance. However, due to development of septicemia, the patient underwent urgent right hemicolectomy. All patients recovered and were discharged during the further course. CONCLUSIONS: Computed tomography is of great value for the diagnosis of cecal diverticulitis and its differentiation from acute appendicitis. Conservative treatment is sufficient in uncomplicated cases, while surgery is reserved for those with associated large abscess or free perforation.

Surface Electromyography Reliably Records Electrophysiologically Evoked Internal Anal Sphincter Activity: A More Minimally Invasive Approach for Monitoring Extrinsic Innervation.

BACKGROUND: Even in the case of minimally invasive pelvic surgery, sparing of the autonomic nerve supply is a prerequisite for maintaining anal sphincter function. Internal anal sphincter (IAS) innervation could be electrophysiologically identified based on processed electromyographic (EMG) recordings with conventional bipolar needle electrodes (NE). This experimental study aimed for the development of a minimally invasive approach via intra-anal surface EMG for recordings of evoked IAS activity. METHODS: Six male pigs underwent nerve-sparing low anterior rectal resection. Electric autonomic nerve stimulations were performed under online-processed EMG of the IAS. EMG recordings were simultaneously carried out with conventional bipolar NE as the reference method and newly developed intra-anal surface electrodes (SE) in different designs. RESULTS: In all experiments, the IAS activity could be continuously visualized via EMG recordings based on NE and SE. The median number of bipolar electric stimulations per animal was 27 (range 5-52). The neurostimulations resulted in significant EMG amplitude increases for both recording types [NE: median 3.0 µV (interquartile range, IQR 2.8-3.5) before stimulation vs. 7.1 µV (IQR 3.9-13.8) during stimulation, p < 0.001; SE: median 3.6 µV (IQR 3.1-4.3) before stimulation vs. 6.8 µV (IQR 4.8-10.3) during stimulation, p < 0.001]. CONCLUSIONS: Intra-anal SE enabled reliable EMG of electrophysiologically evoked IAS activity similar to the conventional recording via NE. The transfer of the method to access platforms for transanal total mesorectal excision or robotics may offer a practical more minimally invasive approach for monitoring extrinsic innervation.

Surgeons' assessment of internal anal sphincter nerve supply during TaTME - inbetween expectations and reality.

BACKGROUND: Intraoperative identification of nerve fibers heading from the inferior rectal plexus (IRP) to the internal anal sphincter (IAS) is challenging. The transanal total mesorectal excision (TaTME) is said to better preserve pelvic autonomic nerves. The aim of this study was to investigate the nerve identification rates during TaTME by transanal visual and electrophysiological assessment. MATERIAL AND METHODS: A total of 52 patients underwent TaTME for malignant conditions. The IRP with its posterior branches to the IAS and the pelvic splanchnic nerves (PSN) were visually assessed in 20 patients (v-TaTME). Electrophysiological nerve identification was performed in 32 patients using electric stimulation under processed electromyography of IAS (e-TaTME). RESULTS: The indication profile for TaTME was comparable between the v-TaTME and the e-TaTME group. The identification of IRP was more meaningful under electrophysiological assessment than under visual assessment for the left pelvic side (81% vs. 45%, p = 0.008) as well as the right pelvic side (78% vs. 45%, p = 0.016). The identification rates for PSN did not significantly differ between both groups, respectively (81% vs. 75%, p = 0.420 and 84% vs. 70%, p = 0.187). CONCLUSIONS: The transanal approach facilitated visual identification of IAS nerve supply. In combination with electrophysiological nerve assessment the identification rate almost doubled. For further insights functional data are needed.

Topography of the extrinsic internal anal sphincter nerve supply during laparoscopic-assisted TAMIS TME: five key zones of risk from the surgeons' view.

PURPOSE: Sparing the extrinsic autonomic innervation of the internal anal sphincter during total mesorectal excision is important for the preservation of anal sphincter function. This study electrophysiologically confirmed the topography of the internal anal sphincter nerve supply during laparoscopic-assisted transanal minimally invasive surgery for total mesorectal excision. METHODS: This prospective study was conducted at two large multispecialty referral centers. Six patients (five males and one female) aged between 45 and 65 years with low rectal cancer (≤5 cm from the anal verge) were enrolled. Surgery was performed under electric stimulation of the pelvic autonomic nerves with observation of the electromyographic signals of the internal anal sphincter. RESULTS: The minimally invasive transanal surgical approach enabled advantageous visualization of the pelvic autonomic nerves in all patients. In particular, extrinsic innervation to the internal anal sphincter near the levator muscle was consciously spared under electrophysiological confirmation. The evoked absolute electromyographic amplitudes of the internal anal sphincter during transanal minimally invasive surgery were significantly lower than the initial results of the laparoscopic approach [3.7 µV (interquartile range 2.4; 5.7) vs. 4.3 µV (interquartile range 3.1; 8.6); p = 0.002]. Five key zones of risk for pelvic autonomic nerve damage were identified. No complications occurred. CONCLUSIONS: The electromyographic results of this preliminary study indicate advantages for sparing the internal anal sphincter innervation during transanal minimally invasive mesorectal dissection considering the specific in situ neuroanatomical topography.

Laparoscopic neuromapping in pelvic surgery: scopes of application.

BACKGROUND: New developments in intraoperative electrophysiological neuromonitoring for conventional surgery are providing further insights into functional neuroanatomy and nerve-sparing in the minor pelvis. The aim of this study was to open up potential scopes of application in laparoscopy. METHODS: Ten patients with different indications for surgery (presacral tumor excision, n = 2; resection rectopexy. n = 2; low anterior rectal resection, n = 2; proctocolectomy. n = 2; abdomino-perineal excision of the rectum, n = 2) were investigated prospectively. The pelvic autonomic nerves were bilaterally mapped by laparoscopic electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Stimulation results were compared to patients' anorectal and urogenital functional outcome. RESULTS: In all the operations laparoscopic neuromapping (LNM) was technically feasible. Laparoscopy enabled excellent visibility of pelvic neural structures for simple and differentiated electric stimulation. In all cases LNM resulted in significantly evoked electromyographic potentials and intravesical pressure rises. The technique facilitated electrophysiological determination of functional neuroanatomical topography in the minor pelvis. The stimulation results were suitable to confirm laparoscopic nerve-sparing and compatible with patients' anorectal and urogenital functional outcome. CONCLUSIONS: LNM is technically feasible and opens up a new dimension for verification of functional nerve integrity. Further developments and investigations are mandatory to evaluate its role for laparoscopic nerve-sparing procedures.

Resection rectopexy--laparoscopic neuromapping reveals neurogenic pathways to the lower segment of the rectum: preliminary results.

PURPOSE: Nerve sparing in functional pelvic floor surgery is strongly recommended as intraoperative damage to the autonomic nerves may predispose to persistent or worsened anorectal and urogenital function. The aim of this study was to investigate the intraoperative neural topography above the pelvic floor in patients undergoing laparoscopic resection rectopexy in combination with electrophysiologic neuromapping. METHODS: Ten consecutive female patients underwent laparoscopic resection rectopexy for rectal prolapse. Intraoperative identification of pelvic autonomic nerves was carried out with a novel intraoperative neuromonitoring system based on electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Neuromonitoring results were compared to patients' preoperative anorectal and urogenital function and their functional results at the 3-month follow-up. RESULTS: Laparoscopy in combination with electrophysiologic neuromapping revealed neurogenic pathways to the lower segment of the rectum during surgical mobilization. In all procedures, intraoperative neuromonitoring finally confirmed functional nerve integrity to the internal anal sphincter and the bladder. Patients with preoperatively diagnosed fecal incontinence were continent at the 3-month follow-up. The Wexner score improved in median from preoperative 4 (range 1-18) to 1 (range 0-3) at follow-up (p = 0.012). Cleveland Clinical Constipation Score improved in median from 10 (range 5-17) to 3 (range 1-7; p = 0.005). In none of the investigated patients a new onset of urinary dysfunction did occur. No change in sexual function was observed. CONCLUSIONS: Laparoscopy in combination with electrophysiologic neuromapping during nerve-sparing resection rectopexy identified and preserved neurogenic pathways heading to the lower segment of the rectum above the level of the pelvic floor.

Intraoperative monitoring of bladder and internal anal sphincter innervation: a predictor of erectile function following low anterior rectal resection for rectal cancer? Results of a prospective clinical study.

BACKGROUND: The objective was to investigate whether two-dimensional intraoperative neuromonitoring (IONM) of pelvic autonomic nerves has the potential to predict erectile function (EF) following surgery for rectal cancer. METHODS: A consecutive series of 17 sexually active male rectal cancer patients undergoing IONM-based nerve-sparing low anterior rectal resection were evaluated prospectively. IONM was performed by electric stimulation of the pelvic splanchnic nerves with concomitant electromyography of the internal anal sphincter and cystomanometry. Sexual function was assessed using a validated questionnaire. RESULTS: The degree of agreement between electromyography-based and cystomanometry-based IONM with postoperative EF was moderate and good (κ = 0.43 and κ = 0.66). Combined assessment yielded the best agreement (κ = 0.76) with sensitivity of 90%, specificity of 86%, positive predictive value of 90%, negative predictive value of 86%, and overall accuracy of 88%, respectively, in terms of prediction of postoperative EF. CONCLUSION: The method may be suitable to predict male EF following rectal resection.

Intraoperative pelvic nerve stimulation performed under continuous electromyography of the internal anal sphincter.

PURPOSE: The aim of this animal study was to investigate the effect of intraoperative pelvic nerve stimulation on internal anal sphincter electromyographic signals in order to evaluate its possible use for neuromonitoring during nerve-sparing pelvic surgery. METHODS: Eight pigs underwent low anterior rectal resection. The intersphincteric space was exposed, and the internal (IAS) and external anal sphincter (EAS) were identified. Electromyography of both sphincters was performed with bipolar needle electrodes. Intermittent bipolar electric stimulation of the inferior hypogastric plexus and the pelvic splanchnic nerves was carried out bilaterally. The recorded signals were analyzed in its frequency spectrum. RESULTS: In all animals, electromyographic recordings of IAS and EAS were successful. Intraoperative nerve stimulation resulted in a sudden amplitude increase in the time-based electromyographic signals of IAS (1.0 (0.5-9.0) µV vs. 4.0 (1.0-113.0) µV) and EAS (p < 0.001). The frequency spectrum of IAS in the resting state ranged from 0.15 to 5 Hz with highest activity in median at 0.77 Hz (46 cycles/min). Pelvic nerve stimulation resulted in an extended spectrum ranging from 0.15 to 20 Hz. EAS signals showed higher frequencies mainly in a range of 50 to 350 Hz. However, after muscle relaxation with pancuronium bromide, only the low frequency spectrum of the IAS signals was still present. CONCLUSIONS: Intraoperative verification of IAS function by stimulation of pelvic autonomic nerves is possible. The IAS electromyographic response could be used to monitor pelvic autonomic nerve preservation.

Extracorporeal Stimulation of Sacral Nerve Roots for Observation of Pelvic Autonomic Nerve Integrity: Description of a Novel Methodological Setup.

INTRODUCTION: Neurophysiologic monitoring can improve autonomic nerve sparing during critical phases of rectal cancer surgery. OBJECTIVES: To develop a system for extracorporeal stimulation of sacral nerve roots. METHODS: Dedicated software controlled a ten-electrode stimulation array by switching between different electrode configurations and current levels. A built-in impedance and current level measurement assessed the effectiveness of current injection. Intra-anal surface electromyography (sEMG) informed on targeting the sacral nerve roots. All tests were performed on five pig specimens. RESULTS: During switching between electrode configurations, the system delivered 100% of the set current (25 mA, 30 Hz, 200 µs cathodic pulses) in 93% of 250 stimulation trains across all specimens. The impedance measured between single stimulation array contacts and corresponding anodes across all electrode configurations and specimens equaled 3.7 ± 2.5 kΩ. The intra-anal sEMG recorded a signal amplitude increase as previously observed in the literature. When the stimulation amplitude was tested in the range from 1 to 21 mA using the interconnected contacts of the stimulation array and the intra-anal anode, the impedance remained below 250 Ω and the system delivered 100% of the set current in all cases. Intra-anal sEMG showed an amplitude increase for current levels exceeding 6 mA. CONCLUSION: The system delivered stable electric current, which was proved by built-in impedance and current level measurements. Intra-anal sEMG confirmed the ability to target the branches of the autonomous nervous system originating from the sacral nerve roots. SIGNIFICANCE: Stimulation outside of the operative field during rectal cancer surgery is feasible and may improve the practicality of pelvic intraoperative neuromonitoring.

Risk Factor Analysis for Newly Developed Urogenital Dysfunction after Total Mesorectal Excision and Impact of Pelvic Intraoperative Neuromonitoring-a Prospective 2-Year Follow-Up Study.

AIM: Urogenital dysfunction is a common sequela following total mesorectal excision for rectal cancer. This prospective study analyzed potential risk factors and investigated the impact of pelvic intraoperative neuromonitoring. METHOD: Included were 85 patients undergoing total mesorectal excision for rectal cancer, 43 under the control of pelvic intraoperative neuromonitoring. Urogenital function was assessed with validated questionnaires within a 2-year follow-up period. Potential risk factors were identified by multivariate analysis. RESULTS: Overall, approximately one-third of treated patients suffered from new onset of urinary dysfunction. Initially, half of the sexually active patients were affected by sexual dysfunction; after 2 years, almost three quarters were affected. In the pelvic intraoperative neuromonitoring group, urinary and sexual dysfunction rates including minor and major disturbances were significantly lower (2-year follow-up 20% vs. 51% (p = 0.004) and 56% vs. 90% (p = 0.010)). Throughout the survey, non-performance of pelvic intraoperative neuromonitoring was found to be an independent risk factor. Neoadjuvant chemoradiotherapy was identified as an independent predictor for urogenital dysfunction in the further course one and 2 years after surgery. CONCLUSION: Pelvic intraoperative neuromonitoring is associated with significantly lower rates of urinary and sexual dysfunction in the short and long run, whereas neoadjuvant chemoradiotherapy has a negative impact only in the long run.

Total mesorectal excision--does the choice of dissection technique have an impact on pelvic autonomic nerve preservation?

BACKGROUND: The aim of this experimental study was to assess the quality of pelvic autonomic nerve preservation of different dissection techniques. MATERIAL AND METHODS: Twelve pigs underwent low anterior rectal resection (LARR) with scissors, ultracision, monopolar diathermy, and waterjet, each in three animals. Assessment of pelvic autonomic nerve preservation was carried out by stimulation of the pelvic splanchnic nerves under electromyography of the internal anal sphincter (IAS). Neurostimulation was performed bilaterally after posterior dissection, after complete mesorectal dissection, and after rectal resection. RESULTS: Stimulation resulted in significantly increased amplitudes of the time-based electromyographic signal of the IAS, confirming nerve preservation. The stimulation results after complete mesorectal dissection showed comparable median amplitude increases for dissection with scissors (10.34 µV (interquartile range [IQR], 5.58; 14.74)) and ultracision (9.79 µV (IQR, 7.63; 11.6)). Lower amplitude increases were observed for monopolar diathermy (4.47 µV (IQR, 2.52; 10.46)) and waterjet (0.61 µV (IQR, 0.07; 2.11)) (p = 0.038). All animals undergoing dissection with scissors, ultracision, and monopolar diathermy had bilateral positive results. Of three animals undergoing LARR with waterjet, one had bilateral positive results. Two had unilateral negative results, indicating incomplete nerve preservation. CONCLUSION: Scissors, ultracision, and monopolar diathermy might have comparable nerve-sparing potentials and differed from waterjet.

Total mesorectal excision with intraoperative assessment of internal anal sphincter innervation provides new insights into neurogenic incontinence.

BACKGROUND: The aim of this prospective study was to assess internal anal sphincter (IAS) innervation in patients undergoing total mesorectal excision (TME) by intraoperative neuromonitoring (IONM). STUDY DESIGN: Fourteen patients underwent TME. IONM was carried out through pelvic splanchnic nerve stimulation under continuous electromyography of the IAS. Anorectal function was assessed with the digital rectal examination scoring system and a standardized questionnaire. RESULTS: Nine of 11 patients who underwent low anterior resection had positive IONM results, with stimulation-induced increased IAS electromyographic amplitudes (median 0.23 µV (interquartile range [IQR] 0.05, 0.56) vs median 0.89 µV (IQR 0.64, 1.88), p < 0.001) after TME. The patients with the positive IONM results were continent after stoma closure. Of 2 patients with negative IONM results, 1 had fecal incontinence after closure of the defunctioning stoma and received a permanent sigmoidostomy. In the other patient the defunctioning stoma was deemed permanent due to decreased anal sphincter function. In 3 patients who underwent abdominoperineal excision, IONM assessed denervation of the IAS after performance of the abdominal part. CONCLUSIONS: This study demonstrated that IONM of IAS innervation in rectal cancer patients is feasible and may predict neurogenic fecal incontinence.