TaTME Combined with IORT for the Treatment of Locally Advanced Rectal 2 Cancer ： A case report

Transanal total mesorectal excision (taTME) which aims to achieve more 26 accurately complete resection of distal mesorectum has arouse much more attention 27 worldwide. TaTME can significantly improve the local control (LC) and overall 28 survival (OS) of the patients with locally advanced rectal cancer. Intraoperative 29 radiotherapy (IORT), also as a emerging treatment method for locally advanced tumors, 30 can lead to the potential for dose escalation, reduce overall treatment time, and increase 31 patient convenience. Our study firstly combined taTME and IORT for the treatment of 32 locally advanced rectal cancer. The tumor involved 60 mm rectal wall and located 30 33 mm from anal margin. TaTME and IORT were successfully achieved in this patient. 34 There was no obvious complications occurred, including the anastomotic fistula. The 35 patient recovered well and further systematic systematic chemotherapy and 36 radiotherapy were suggested. We conclude that taTME with low-energy X-rays IORT 37 may not only benefit the circumferential resection margin (CRM) but also improve the 38 local control (LC) for the patient with locally advanced rectal cancer. 39


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Colorectal adenocarcinoma is the third most common cancer worldwide and the 44 total mesorectal excision (TME) rule is a gold standard of surgery to achieve negative 45 distal resection margin (DRM) and circumferential resection margin (CRM) which are 46 closely associated with local recurrence (LR) and disease-free survival (DFS) [1,2] . 47 Medium or lower rectum cancer is often a challenge for surgeons to take the surgical 48 dissection due to the limited width of distal pelvis and with the difficulties in 49 visualization. Especially, narrow male pelvis, high body mass index (BMI), bulky 50 tumors, visceral obesity, locally advanced tumors, has been identified as risk factors 51 predicting intraoperative difficulty and potentially leading to a poor oncology specimen. 52 Due to the limited field of vision, laparoscopic or open TME is difficult to 53 identify the resection of DRM, which may lead to the risks of uncomplete TME or 54 positive CRM in paitens with above factors. Furthermore, in the narrow pelvis, 55 endoscopic stapler is not flexible and usually requires multiple stapler firings, which 56 will lead to angulated and crossing staple lines, increasing the risk of anastomotic 57 leakage [3] . To overcome these chanllenges and combinie the concept of Natural Orifice 58 Transluminal Endoscopic Surgery (NOTES) and Transanal Endoscopic Microsurgery 59 (TEM), transanal TME (taTME) aiming to achieve more accurately complete resection 60 of distal mesorectum was firstly introduced by Sylla [4] and has been arouse a great deal 61 of attention. 62 Although the rate of LR has been obviously reduced with the TME surgery, LR 63 rate of locally advanced cancer is still higher. Furthermore, the achievement of 64 complete surgical excision and margins is significant, multiple modalities involving 65 surgery, external beam radiotherapy, and chemotherapy are still required. Nowadays, to 66 improve LR and avoid the risks related to preoperative external beam radiotherapy 67 (EBRT), intraoperative radiotherapy (IORT)，as a part of multimodality treatmet, 68 allows the precise delivery of a large tumoricidal dose to the target areas to reduce the 69 LR [5] during operation. Compared with external beam radiotherapy, the advantages of 70 IORT include the potential for dose escalation, reduced overall treatment time, and 71 increased patient convenience. Especially, the main advantage of IORT is sterilizing 72 close or positive resection margins.

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Recently, compared with intraoperative electron radiation therapy (IOERT) which 74 is delivered in special shielded operating rooms [6] and higher surface dose of high-75 dose rate brachytherapy (HDR-IORT) [7] , the mobile device of INTRABEAM IORT 76 that emits low-energy (50 kV) photons at a high dose-rate and modulates the electron 77 beam to soft x-ray in a uniform dose [8] has been widely used in tumors of breast, rectum, 78 brain, and vertebrae. INTRABEAM mobile IORT could precisely administer high dose 79 of radiation to the at-risk areas while concurrently minimizing exposure to surrounding 80 structures (bowel, bladder) to optimize the local effects of radiotherapy [9] .

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To overcome the higher positive rate of CRM and improve the local control (LC), 82 we take the advantages of taTME and INTRABEAM IORT using low-energy X-rays 83 to provide a new treatment modality in locally advanced patiens with above risk factors.

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As far as we know, our study is the first report of this novel treatment modality and the 85 purpose of this study is to demonstrate our preliminary experience.   our medical team planned to take the taTME surgery combined with IORT using low-103 energy X-rays after the patient signed the consent form.   2) The origin of inferior mesenteric artery (IMA) was ligated and 123 lymphadenectomy around IMA was done after patient was placed in the right-head-124 ventral position to achieve optimal view of the left colon. (    The dissected rectal specimen was photographed ( Figure 3E). were put to isolate and protect the adjacent structures from radiation ( Figure 3H).  should be provided.

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TaTME includes the''push me-pull you'' and "bottom-to-up" approaches, which 183 allows two-team synchronous collaboration to further shorten the operation time [11] .

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The ''push me-pull you'' approach can afford the crucial medial retraction of the 185 mesorectum to secure sexual function by providing better visualization of the pillars, 186 plexuses, and neurovascular bundles [12] . The "bottom-to-up" approach makes the 187 dissection more easily and efficiently by overcoming the limitations [13] and also allows 188 for no need for an extra abdominal assist incision. Furthermore, cutting specimen in 189 vitro can avoid multiple stapler firings to reduce the incidence of anastomosis 190 leakage [14] .

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When the abdominal dissection completed, based on the transanal approaches of 192 deep pelvic dissection, laparoscopic-assisted taTME can identify the resection plane 193 clearly to achieve a beeter visualization of distal rectum and more clearly distal 194 resection margin to assure the safety of CRM in these challenging patients [15] . In a RCT 195 comparing taTME to laparoscopic TME in 100 patients with low rectal cancer, Denost 196 et al [16] revealed lower positive CRM rates in taTME group (4%) than that in 197 laparoscopic TME group (18%). TaTME can also reduce the rate of coversion to open 198 surgery with only 0-9.1% in taTME cases, which is much more lower compared with 199 that in laparoscopic TME cases in COLOR II [17] . of the urethra and urethral sphincter [26] , which not commonly occurred in laparoscopic No matter the taTME surgery or the IORT, we should pay attention to the anorectal 265 function, especially the bowel frequency and fecal incontinence. TaTME transanal 266 approach may bring injury to the intersphincteric resection [27] and the radiotherapy may 267 induce the fibrosis around rectum affecting the compliance of rectum [28] . Both of them 268 may lead to the low anterior resection syndrome (LARS), a complex of symptoms 269 consisting of incontinence for flatus and /or feces, constipation, urgency, and bowel 270 movements [29] . In our study, the anorectal function should be investigated after the 271 return of ileostomy.

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Although the lack of special pneumatic machine to maintain the stable pressure 273 in transanal procedure, we used the plastic bag to connect the laparoscopic pneumatic 274 machine to the transanl operation platform to obtain a stable pressure. Furthermore, the 275 anus could be exposed by sutures instead of Longstar retractor to achieve optimal 276 operation field. To our knowledge, our study is the first to report the taTME with 277 INTRABEAM IORT using low-energy X-rays in locally advanced low rectal cancer, 278 and several advantages of the treatment modality was concluded as follows.

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Firstly, taTME benefits in achieving a good oncology specimen and lowering the  Therefore, when encounters the challenging male and fat patients with narrow 291 pelvis in locally advanced rectal cancer, taTME with low-energy X-rays IORT may not 292 only benefit the CRM but also improve the LC.

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In this study, we report the first case of locally advanced rectal cancer who 294 underwent the combined therapy of hybrid taTME and INTRABEAM IORT. We took 295 the advantages of these two methods. The anus of this patient was successfully 296 preserved and no obvious complications, including the anastomotic fistula, occurred.

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The patient recovered well and further systematic systematic chemotherapy and 298 radiotherapy were received. And, until now, there is no sign of postoperative recurrence.  Consent for publication 310 Written consent was obtained from the patient for publication of this study and 311 accompanying images.

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Availability of data and material 313 The datasets used and/or analyzed during the current study are available from the 314 corresponding author on reasonable request.

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Competing interests 316 The authors declare that they have no competing interests.