Robotic surgery in Hirschsprung disease: a unicentric experience on 31 procedures

Robotic surgery has been increasingly applied to Hirschsprung patients with encouraging results. We report the results of a 5 year unicentric experience. All consecutive HSCR patients older than 12 months who underwent a surgical procedure with robotic approach between September 2017 and August 2022 were prospectively included. We collected data regarding demographics, extent of aganglionosis, associated anomalies, indications to surgery, and a number of perioperative data such as surgical details, intraoperative and perioperative complications, length of surgery, length of hospital stay, and functional outcome. A total of 28 patients underwent 31 robotic procedures during the study period. Median age at surgery was 82 months. Eleven primary Totally Robotic Soave Pull-Through, 12 redoes, 5 innervative mapping, 2 redundant rectal pouch excision, and 1 Miles’ procedures have been performed. Median console time was 145 min. No conversion to either laparoscopy nor to laparotomy was required. Median length of hospital stay was 6 days. Two patients experienced complications requiring reiterative surgery. One patient experienced mild postoperative enterocolitis. Normal continence was achieved by 70% of patients after a median of 16 months postoperatively (80% for primary pull-throughs, 55% for redoes). To conclude, robotic surgery for older HSCR patients proved to be feasible, safe, and effective. Patients with complex surgical requirements seem to benefit most from this promising approach. Provided the economic burden is addressed and solved, robotic surgery will represent an excellent alternative for the surgical treatment of HSCR patients.


Introduction
Since early 2000, minimally invasive surgery gained popularity in the treatment of Hirschsprung's disease (HSCR) with good results and the well-known advantages of minimally invasive surgery [1,2]. With the exception of a single experience in adults, dating back to 2013, robotic surgery in HSCR has been first reported in children by our group in 2017 and later on with an extended series, in 2020. We could confirm safety and feasibility of totally robotic Soave procedure (TRSPT) in HSCR along with its promising results in terms of functional outcome [3,4]. Given the versatility of robotics in children [5], indications have been subsequently extended to other procedures performed in HSCR patients and we now routinely resort to robotic approach for various procedures, including redo pull-throughs [6]. This paper aims at reporting the results of our unicentric experience with robotic surgery applied to pediatric HSCR patients to address indications and possibly suggest specific recommendations in such a dedicated and rare setting.

Materials and methods
Given the referral role of Umberto Bosio Center for Digestive Diseases, a number of HSCR patients are seen and diagnosed beyond 12 months of age in our Institution. Whenever feasible, those patients are scheduled for a robotic approach. Based on these considerations, all consecutive HSCR patients who underwent a surgical procedure with robotic approach at the Umberto Bosio Center for Digestive Diseases, The Children Hospital, Alessandria, between September 2017 and August 2022 (5 years) have been prospectively included. Ethical Committee approval was obtained on June 15, 2017, ID ASO. CHIRT.17.01.

Confirmation of HSCR diagnosis
In case of patients undergoing a primary pull-through, two experienced pathologists (PN and SC) confirmed the diagnoses on rectal suction or surgical biopsies (based on age) performed in our Center and stained with enzymohistochemistry as previously reported [7]. In case of patients already operated on elsewhere who presented with persistent obstructive symptoms, both pathologists re-assessed the slides belonging to previous samples stained with conventional histology, enzymohistochemistry or immuno-histochemistry to confirm the exact HSCR diagnosis.

Diagnostic workup
After confirming the diagnosis of HSCR, each patient underwent a comprehensive diagnostic workup including barium enema and clinical phenotype assessment (kidney and urinary tract and cardiac ultrasound scans and audiometry), as reported in our previous reports [8,9], molecular genetics, and all further investigation according to specific clinical features.

Collected data
A number of data have been collected prospectively according to data protection Act. Demographic data, extent of aganglionosis, associated anomalies, indications to surgery (primary or redo and indications for redoing), and a number of perioperative data, such as surgical details, intraoperative and perioperative complications, length of surgery, length of hospital stay, and functional outcome were assessed in all outpatient visits, the last being recorded for outcome analysis.

Follow-up protocol
Postoperatively, follow-up was performed in an outpatient setting after 1 month, 3 months, 6 months, 12 months, 18 months, and then yearly based on patients' clinical conditions. Presence of constipation, enterocolitis occurrences (HAEC), continence, and perianal excoriations have been assessed.

Definitions [8]
• Extent of Aganglionosis • Classic HSCR-Aganglionosis extending up to the splenic flexure • Long HSCR-Aganglionosis extending beyond the splenic flexure but confined within ascending colon • Ultralong HSCR or TCSA-Aganglionosis extended to the terminal ileum with variable small bowel involvement • Continence-Continence was assessed in patients older than 4 years of age, without intellectual disability and a minimum 6 months of follow-up according to modified Wingspread scoring system. Continence was graded into Excellent, Good, Fair, and Poor [10] and was assessed at the last outpatient examination. • Enterocolitis (HAEC)-Defined according to Pastor criteria [11] and graded according to Elhalabi criteria (mild, moderate, severe) [12] • Constipation-According to Rome IV criteria [13,14] • Perineal rash-severe perineal excoriation that interferes with a normal quality of life lasting longer than 6 weeks and requiring medications or change of diet.

Statistical analysis
Descriptive statistics were reported as absolute frequencies and percentages. Median and ranges were used to describe semiquantitative and quantitative variables. Mean and standard deviation were used to report continuous variables.

Demography and phenotype
Out of 316 HSCR patients who are being treated at the Umberto Bosio Center for Digestive Diseases since 2017, 161 have been admitted to the Pediatric Surgical Unit and 92 underwent a pull-through or other diagnostic and continence procedures for a total amount of 111 major surgical procedures (excluding stoma fashioning and reversal).
In particular, during the study period, 28 of the abovementioned HSCR patients older than 12 months of age underwent 31 robotic procedure that represent the focus of present study. Male-to-female ratio was 4.6:1. Median age at surgery was 82 months (ranging between 12 months and 17 years). Median weight at surgery was 23 Kgs (ranging between 9 and 72 Kgs). Nineteen patients suffered from Classic HSCR, 7 from Long HSCR, 2 from TCSA. No familial cases were recorded. Thirteen associated anomalies were detected in 11 patients (39%) including 4 Down Syndrome, 2 congenital anomalies of the kidney and urinary tract, 1 Ondine's Course, 1 Brugada's syndrome, 1 congenital heart disease, 1 cerebral palsy, 1 congenital immune deficiency, 1 skeletal abnormality, and 1 eosinophilic colitis.

Surgical procedures
• Totally Robotic Soave Pull-Through (TRSPT)-A total of 11 patients underwent a TRSPT, including 2 TCSA, 1 Long HSCR, and 8 Classic HSCR. • Redo Totally Robotic Soave Pull-Through (Redo TRSPT)-A total of 12 patients underwent a Redo TRSPT, including 2 Long HSCR and 9 Classic HSCR. All patients but one had been operated elsewhere for first surgeries. In all cases, first surgery was an endorectal pull-through, either laparotomic or laparoscopic. None previously underwent surgery with robotic approach. • Robotic innervative mapping-A total of 5 patients underwent innervative mapping, including 1 Long HSCR and 4 Classic HSCR. In all cases, mapping was indicated for persistent obstructive symptoms due to suspected persistent innervative issue. • Redundant Rectal Pouch Excision-A total of 2 patients underwent a Robotic Redundant Rectal Pouch Excision, both suffering from Long HSCR. • Robotic Proctocolectomy and Miles' procedure-One patient with complete anal canal fibrosis and severe stricture due to multiple perianal abscesses underwent radical proctocolectomy and modified Miles' procedure.

Surgical details (robotic platform Da Vinci Si)
Trocar and patient positioning is similar for all the procedures as surgery aims at negotiating the deep pelvis. Patients are kept in slight Trendelenburg positioning (9 degrees) the remaining aspects being described in our previous reports [3,4]. In case of colonic mapping, trocars are placed as described above, but no Trendelenburg position is used to facilitate colonic manipulation. Details of surgical procedures performed with robotic approach are reported below.
• TRSPT and Redo TRSPT (23 procedures, Fig. 1a and b)-Those procedures have been performed according to our previous reports [3,4] regardless of the presence of a stoma or extent of aganglionosis as the pelvis and rectal dissection represented the focus and goal of robotic surgery. A stoma was already in place in 4 patients and was maintained to protect the anastomosis up to 6 weeks postop. A protective stoma was fashioned at time of surgery in a further 6 patients with the same timing for subsequent closure. Based on those data, a total of 10 patients (45%) received a stoma as part of the treatment (4 TRSPT and 6 redo TRSPT). • Robotic Innervative mapping (5 procedures, Fig. 2)-These procedures consisted in identification of the peritoneal reflection, freeing of a few centimeters of the rectum extraperitoneal rectum, seromuscular biopsy taken at the reflection, 5 cm above and a further 5 cm above to provide mapping of the last 10 intraabdominal centimeters of colon. In case of suspected complex innervative issue, two further biopsies were taken at the transverse colon and at the caecum. All biopsy sites were closed back with interrupted Prolene 4-0 sutures and a final hydrostatic check of the seal of the enterotomies was performed before dedocking.  , Fig. 4)-The procedure has been performed in a patient who previously experienced two pull-through procedures (Duhamel and Swenson) and subsequently developed severe anal fibrosis, multiple recurrent perianal abscesses, and anastomotic retraction.
The procedure consisted in robotic radical proctocolectomy resembling the technical features of both TRSPT and redo TRSPT. The colon that was previously pulledthrough (right ascending colon) was isolated downwards to the elevator ani (1-2 cm above the dentate line) with a delicate and extremely demanding dissection due to severe pericolic fibrosis and an evident "frozen pelvis". Transanal distal dissection allowed the removal of the colon. A previously fashioned ileostomy was left in place as definitive stoma. The anus was closed in layers with three consecutive pure-string sutures and a drain was left from above (Fig. 4).  Table 1 for details regarding each procedure).

Outcome (overall series)
• Intraoperative complications-Two patients experienced mucosal tearing during endorectal dissection with subsequent fecal contamination of surgical field. One of these patients, who had a stoma already fashioned preoperatively, maintained the stoma in place for 6 weeks to promote healing and avoid anastomotic leakage. None of the further intraoperative complications have been experienced. No conversion to either laparoscopy nor to laparotomy was required. • Postoperative complications-Six patients experienced postoperative complications. Of these, 2 were Clavien-Dindo 1 (2 severe perineal rashes), 2 were Clavien-Dindo 2 (bowel obstruction and residual innervative issue), and 2 were Clavien-Dindo 3b complications (bowel obstruction due to cuff stricture and anastomotic leakage requiring surgical treatment, namely stenotic cuff release with temporary stoma fashioning and redo pullthrough, respectively) [15,25]. • Adequacy of biopsies for innervative mapping-All biopsies proved sampled with robotic approach proved to be adequate for both diagnosis and exclusion of innervative issues. • HAEC-1 out of 23 patients who could be assessed on this regard experienced mild postoperative HAEC • Constipation-3 out of 23 patients who could be assessed on this regard experienced constipation requiring medical treatment with softeners. Fig. 4 Anus closed in layers at the very end of the Miles' procedure performed to deal with a severe pelvi/perineal fibrosis after multiple procedures performed in a male patient with HSCR. A further redo was not feasible and the previously pulled-through colon had to be removed to get rid of the continuous discharge related to a severe diversion colitis o TRSPT-Excellent to good in 4/5 (80%). p Redo TRSPT-Excellent to good in 5/9 (55%). q Redundant rectal pouch excision-Excellent to good in 2 (100%).

Discussion
This is one of the largest series addressing the use of robotic surgery for the treatment of HSCR. The results of our series confirmed what previously suggested by our group [3,4] regarding safety and feasibility of this approach for "older" HSCR patients. We could also demonstrate the intriguing versatility of the Da Vinci Si robotic system as HSCR patients could undergo a variety of different surgical procedures ranging from diagnostic biopsies for innervative mapping to primary therapeutic or complex reconstructive procedures.
Minimally invasive colonic mapping in HSCR has been first reported by Mazziotti and Carvalho in 2001 [16, 17] with good results but in a relatively small series of patients. Later on, in 2021, Bogusz et al. reported similar results and outcome in a slightly larger series [18]. These authors reported safety and reliability of a minimally invasive approach for the diagnosis of intestinal innervative issues in HSCR. In accordance with what previously published, our series of patients confirmed how helpful minimally invasive surgery is in the diagnostic workup of HSCR patients who experience postoperative obstructive symptoms. In particular, we could demonstrate that the robotic system is versatile, safe, and effective in harvesting adequate size biopsies with minimal to no risk of postoperative complications, leakage in particular. In fact, we showed that enterotomy closure with interrupted sutures is straightforward, safe and effective with the possibility of early discharge, minimal postoperative requirements, and the possibility to reestablish rectal irrigation shortly after surgery. Biopsy size and depth, which represent a critic aspect of adequate colonic biopsies, proved to be consistently adequate thanks to the magnification and 3D vision, thus increasing the likelihood of adequate sampling (Fig. 2).
Even if innervative mapping proved to benefit from this approach, the biggest advantages of robotics should be more evident for procedures involving deep pelvic structures. Hebra in 2011 and Rickey in 2013 proved that the use of Da Vinci robotic system is feasible and safe for both infants and adults with HSCR [19,20]. Of note, the authors performed a Swenson procedure and not to a Soave endorectal pullthrough, in infants [19]. Both papers confirmed safety and feasibility of robotics for complex reconstructive surgeries in HSCR suggesting the possibility for a larger adoption of robotics in pediatric surgical practice. This is confirmed by the results of our series of patients who underwent complex pelvic reconstructive procedures. More recently, Quynh and co-workers reported intriguing results of a large series of 55 patients who underwent robotic Soave procedures. Noteworthy, even this publication seems to refer to Soave-Georgeson procedures more than to a true Soave with robotic seromuscular dissection as the Authors report "…around the rectal wall was performed circumferentially down to the pelvis under the peritoneal reflection approximately 2 cm anteriorly and the level of the coccyx posteriorly" [21].
The first reported series of Totally Robotic Soave Pull-Through (TRSPT) has been published by our group in 2017 [4]. Since then, we increased the number of patients who underwent TRSPT primary and redo procedures [3]. Our series now counts a total of 23 procedures, performed in children older than 12 months, with intriguing results. Duration of surgery proved to be longer compared to what observed in conventional laparoscopic or open approaches, with console time lasting an average of 2 h. Interestingly, surgery proved to last longer in primary TRSPT compared to redo TRSPT. Also, complication rate proved to be reasonable with most issues occurring in patients undergoing multiple reiterative procedures. Even if these differences and trends proved not to be statistically significant, the shorter length of surgery observed in redo TRSPT suggested that magnification, 3D view, and increased dexterity of robotic arms could be particularly helpful in dissecting tissues in delicate and deranged regions with fibrosis and inflammation, as found in previously operated HSCR patients.
If we consider that our series of HSCR patients included only those older than 12 months of age at surgery (median age close to 7 years), functional outcome proved to be promising with a very low rate of constipation and postoperative HAEC and an intriguing 80% of excellent-to-good continence for primary TRSPT after a median of 1 year postoperatively. The enthusiastic outcome reported in a recent publication by Delgado and co-workers addressing infants younger than 12 months [22] suggests that robotic approach could represent a valid alternative for all HSCR patients, even infants younger than 12 months of age. As expected and previously reported [23], continence proved to be worse in those patients who underwent a redo. Anyway, it is well known that continence normalization can be observed up to 4 years postoperatively [23], so we still expect an improvement that will be addressed in the long term.
The versatility of robotic surgery applied to HSCR patients was confirmed by the possibility to perform unconventional or uncommon procedures such as excision of the redundant rectal pouch or radical proctocolectomy with Miles' procedure. Both proved to be feasible and safe with reasonable length of surgery and excellent postoperative recovery (Table 1). This aspect has been confirmed by the absence of complications in this specific subset of patients who underwent surgery with minimal requirements, short hospitalization, and rapid recovery of daily activities.
Technical advantages of robotic surgery over laparoscopy have been already addressed, yet it is difficult to report a superiority of one approach over the other with relation of the overall outcome. This is due to the combination small series of patients and relatively low complication rates observed in most pediatric surgical fields. These issues make it difficult to detect statistically significant differences and identify suitable subgroups of patients, risk factors, and correct indications. Previous publications demonstrated that in face of similar outcomes, length of surgery and costs of robotic surgery are so high to limit its spread and routine use in pediatric surgical practice [5,24,25].
Our study have several limitations: (1) A number of bias, including wide age-range, heterogeneous clinical features, and proposed surgical procedures, limited the interpretation of our results; (2) even if larger than others, this series remain too small to reliably assess any outcome measure; (3) the DaVinci Si surgical system has now been overcome by the Xi version that improved most of technical aspects and limitation of the platform making our results only partially reproducible.
Based on these considerations, we could not address the question regarding the superiority of robotic approach over laparoscopy for HSCR patients. Anyway, we could speculate that a specific subgroup of them could benefit from the advantages of robotic systems. Older and plurioperated patients undergoing complex pelvic reconstructions are those who seem to benefit most from this approach. The increased dexterity improves daintiness of tissue handling, reliability of enterotomy suture-closure, and magnification to perform adequate size biopsies. This suggests that also innervative mapping might benefit from a robotic approach, but larger series and possible randomized trials are needed to address this specific aspect.
To conclude, robotic surgery in older HSCR patients confirmed to be feasible and safe. In particular, older children with previously operated deep pelvis and complex surgical requirements seem to benefit most from this promising approach. Provided the economic burden is addressed and solved, robotic surgery will represent an excellent alternative for the surgical treatment of HSCR.
Author contribution GM, ME, EF, and MPD: drafted the paper. SC: revised all histology and confirmed the diagnosis and possible need for redoing due to innervative issues. TM and VB: participated in enrolling the patients. JB and AT: performed all preoperative radiological investigations required to determine the need for surgery. APP: conceived the study and performed all surgical procedures. All authors revised and approved the final version of the paper.

Funding
The authors have not disclosed any funding.