Transanal endoscopic cooperative surgery as a less invasive resection technique for anorectal tumors extending beyond the dentate line: Case series

Keywords

Endoscopy Lower GI Tract - Endoscopic resection (polypectomy, ESD, EMRc, ...) - Polyps / adenomas / ... - Colorectal cancer - Quality and logistical aspects - Performance and complications

Introduction

Endoscopic submucosal dissection (ESD) is indicated for early-stage colorectal tumors; however, the complete resection rate is unsatisfactory (53.3%) for rectal tumors extending beyond the dentate line [1]. Moreover, tumors that require skin excision cannot be resected by ESD alone. Meanwhile, surgical local excision (LE) is indicated for noninvasive tumors located between the external anal canal and lower rectum extending to an anal verge (AV) < 8 cm. However, among LE techniques, transanal excision (TAE) has a higher local recurrence rate for lesions extending to the lower rectum because of poor visualization of the lesion margin [2]. Moreover, transanal endoscopic microsurgery (TEM) can help confirm resection margins of rectal tumors endoscopically; however, removal of lesions close to the AV is technically challenging because of scope fixation to the anal canal [3].

Therefore, optimal resection strategy for tumors broadly extending beyond the dentate line is not well-established. An advantage of ESD is its precise incision of a tumor margin under endoscopic view, and an advantage of LE is its ability to excise skin beyond the dentate line. Thus, we hypothesized that combining ESD and LE could be effective for excising tumors broadly extending beyond the dentate line. We dubbed this combination therapy as transanal endoscopy cooperative surgery (TaECS) and examined its usefulness in this study.

Patients and methods

Study design

In this case series, consecutive patients who had undergone TaECS at a Japanese tertiary cancer center between January and December 2022 were enrolled. We evaluated lesion characteristics and clinical outcomes based on data obtained from medical records and the patient database.

This study was approved by the Ethics Committee of Shizuoka Cancer Center Institutional Review Board, Shizuoka, Japan (No. J2023-175-2023-1) and was performed according to the 1964 Helsinki Declaration and its subsequent amendments. Written informed consent for interventions was obtained from all participants before undergoing treatment.

Indication for TaECS

TECS was indicated for local resection of tumors extending beyond the dentate line with a low risk of lymph node metastases (LNM), which could not be resected by ESD alone due to the requirement for skin excision or by surgical LE alone due to indeterminate lesion extent on the oral side under direct observation. Preoperative examination was performed using a high-resolution endoscope with a magnification function (CF-HQ290ZI, PCF-H290ZI; Olympus Co., Ltd., Tokyo, Japan). Preoperative diagnosis was based on magnifying endoscopy with narrow-band imaging (ME-NBI) and chromoendoscopy findings. To confirm the extent of tumor in the horizontal axis, tumor margins were carefully evaluated, and biopsies were taken from outside the lesion to ensure the resection margin in cases where the lesion extent was indeterminate. Furthermore, we estimated lesion depth using contrast-enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) to confirm absence of LNM and distant metastases. In all cases, a consensus was reached prior to performing a procedure at a cancer board conference attended by endoscopists, gastrointestinal surgeons, gynecologists, dermatologists, and oncologists.

Set-up for TaECS

TaECS was performed in an operating room after ensuring adequate bowel preparation. TaECS was initiated by endoscopic procedure with left lateral decubitus under intravenous (IV) anesthesia. Subsequently, surgical procedure was performed via lithotomy or jack-knife position in general anesthesia.

Endoscopic procedure

Endoscopic procedure was performed using a colonoscope with a water-jet system (PCF-H290T; Olympus Co, Ltd.) fitted with a clear distal attachment, a standard electrosurgical generator (VIO300D; Erbe Elektromedizin GmbH, Tuebingen, Germany), and carbon dioxide insufflation. Prior to resection, tumor margins were confirmed by the endoscopic view or the biopsy scar, and markings were made by cauterization. Endoscopic procedure was performed similarly to ESD. A mucosal incision was made on the oral side, and submucosal dissection was performed as far as possible toward the dentate line.

Surgical procedure

The resection line on the anal side was marked under direct vision. A perianal skin incision was made with a negative margin of at least 1 cm to avoid burning effect to the tumor. The tumor was dissected toward the oral side above the external anal sphincter muscle using the 20W pure-cut mode and coagulation of 20W FULGRATE, an electrosurgical unit (Force Fx-CS; Valleylab, Medtronic plc, Dublin, Ireland). Further dissection was extended into the anal canal on the oral side, where dissection had been performed endoscopically. In cases involving extensive skin excision surrounding the perianal area, the defect was repaired with a skin flap by bilateral V-Y advancement flaps reconstruction to prevent anal canal stricture. The V-Y technique was used to advance flaps as superomedially as possible, and donor sites were closed. Furthermore, flaps were slid toward the anal canal and sutured to the distal end of the rectal mucosal flap. In addition, when the defect involved the vagina or urethra, the flaps were sutured to the mucosa ([Video 1]).

Trans-anal endoscopic cooperative surgery (TaECS); less invasive resection technique for a tumor extending beyond the dentate line (Case 2).Video 1

Postoperative management for TaECS

Broad-spectrum antimicrobials were administered for 1 to 5 days routinely and oral intake was initiated by fasting for 3 to 5 days postoperatively. Moreover, a urethral catheter was placed in lesions where the reconstructed area extended to the vulva.

Pathological assessment

Resected specimens were extended on a panel using pins, fixed in 10% buffered formalin, cut into 3- to 5-mm sections, embedded in paraffin, and sliced at a 3-μm thickness. All samples were histologically assessed by more than two experienced pathologists according to the Japanese Classification of Colorectal Appendiceal, and Anal Carcinoma (July 2018, Ninth Edition) or the International Federation of Gynecology and Obstetrics staging for carcinoma of the vulva (2021).

Clinical outcomes of TaECS

TaECS was performed in three cases, as demonstrated in [Fig. 1]. Patient and lesion characteristics and clinical outcomes are summarized in [Table 1]. In all cases, en bloc resection was achieved. The horizontal margin was indeterminate in one case. No postoperative stricture, delayed bleeding, or anorectal functional disorder was observed.

Fig. 1 Scheme of trans-anal endoscopy cooperative surgery (TaECS).

Table 1 Patient and lesion characteristics.

	Age (years)	Sex	Location	Size* (mm)	En bloc resection	Procedure time (minutes)	AEs	Resection margin	Pathology	p-Stage	Recurrence†
AE, adverse event; p-Stage, pathological stage; SCC, squamous cell carcinoma. *Preoperative lesion size. †Recurrence was evaluated in the latest surveillance.
Case 1	74	Male	Rb	70 mm	Yes	287	No	Horizontal margin indeterminate	Adenocarcinoma	pTisN0M0	None at 17 months
Case 2	58	Male	Anal	20 mm	Yes	341	No	Free	Adenocarcinoma with pagetoid spread	pT1N0M0	None at 27 months
Case 3	73	Female	Vulva	42 mm	Yes	469	Abscess	Free	SCC with lichen sclerosis pT1bN0M0	pT1bN0M0	None at 26 months

Case 1

A 74-year-old man presented with a rectal tumor that had been repeatedly prolapsing out of the anus. A colonoscopy showed a 70-mm villous tumor in the lower rectum ([Fig. 2] a). The tumor was in the anal canal with a flat elevated area extending to the rectum. NBI revealed irregular surface pattern, which was classified as Japan NBI Expert Term Classification (JNET) Type 2B ([Fig. 2] b). CT revealed that the tumor filled in the rectum without LNM or distant metastases. Endoscopic resection of the anal side of the tumor that prolapsed out of the anus was deemed difficult ([Fig. 2] c), as was recognizing the flat elevated area in the rectum side by LE alone due to its large volume. Abdominoperineal resection (APR) could ensure complete removal of the tumor but was considered too invasive for early-stage malignancy. Therefore, TaECS was indicated ([Fig. 2] d). Procedure time was 287 minutes (ESD: 221 minutes; LE: 68 minutes). Histological examination revealed a well-differentiated intramucosal tubular adenocarcinoma without lymphovascular invasion (LVI) ([Fig. 2] e, [Fig. 2] f). The horizontal margin on the anal side was not visualized because of the burning effect, and vertical margins were negative. No recurrence or metastasis was observed at 17-month follow-up ([Fig. 2] g).

Fig. 2 Case 1. a 70-mm sessile rectal tumor extending into the anal canal. b Magnifying endoscopy with narrow-band imaging (NBI) showing irregular villous structures on the top part of the lesion, corresponding to the Japan NBI Expert Team (JNET) classification type 2B. c Tumor prolapsing out of the anus. d Defect after resection with no residual lesion. e Macroscopic view of specimen before fixation with formalin. The blue line indicates well-differentiated intramucosal tubular adenocarcinoma. f Histological examination confirming the diagnosis of well-differentiated tubular adenocarcinoma that was entirely intramucosal. g Endoscopic view of the scar 17 months after treatment.

Case 2

A 58-year-old man with complaints of anal pain was referred to our institution. A 20-mm tumor extending into the anal canal with reddish skin was observed ([Fig. 3] a, [Fig. 3] b). Colonoscopy showed no visible lesion in the rectum ([Fig. 3] c). However, ME-NBI revealed a circumferentially irregular surface pattern extending continuously from the perianal tumor ([Fig. 3] d). Biopsy confirmed a diagnosis of adenocarcinoma with pagetoid cells. The area with the irregular surface on NBI was diagnosed as a pagetoid spread. CT and MRI revealed a 20-mm intraepithelial tumor without LNM and distant metastases. Thus, local resection was indicated for the tumor. Pagetoid spread was difficult to detect macroscopically on the rectum side. Therefore, determining the resection margin by LE alone was considered difficult. Therefore, TaECS was performed to ensure negative margins on the oral side. The defect was repaired with a skin flap. Procedure time was 341 minutes (ESD: 87 minutes; LE and reconstruction: 254 minutes). Gross examination showed a flat, elevated, 20-mm tumor ([Fig. 3] e). Histological assessment confirmed mucinous adenocarcinoma that was invasive to just above the internal anal sphincter (pathological T1) without LVI. Pagetoid spread was observed broadly around the tumor ([Fig. 3] f, [Fig. 3] g). No recurrence or metastasis was observed at 27-month follow-up.

Fig. 3 Case 2. a Endoscopic view of the perianal skin. A flat elevated tumor tinged with white and pink was observed under the perianal skin and extending into the anal canal. b Narrow-band imaging showing dilated crypt openings on the lesion (red arrowhead). c Retroflex endoscopic view with white light imaging showing no visible lesions in the rectum. d Magnifying narrow-band imaging revealing dilated crypt openings and irregular surface pattern (red arrowhead). e Gross examination of the specimen revealing a flat elevated tumor with no visible pagetoid spread. f Macroscopic view of the specimen after fixation with formalin with tumor mapping of the lesion confirming the diagnosis of mucinous adenocarcinoma (red line) and pagetoid spread (green line). g Histological examination indicative of 20-mm mucinous adenocarcinoma with pagetoid spread (blue box; pagetoid cells).

Case 3

A 73-year-old woman with irregular genital bleeding was referred to our institution. A reddish tumor was observed on the vulva, extending into the anal canal ([Fig. 4] a). The lesion had irregular dilated vessels spread toward the anal canal on ME-NBI ([Fig. 4] b, [Fig. 4] c). Biopsies revealed vulvar squamous cell carcinoma (SCC) arising from lichen sclerosis. CT and MRI revealed that the tumor did not extend to adjacent perineal structures and no metastases were detected. Thus, radical vulvectomy was indicated for the tumor. Considering the risk of developing SCC among women with lichen sclerosis [4], complete resection of the area of lichen sclerosis was required. However, margins of the lichen sclerosis could not be determined, even on ME-NBI ([Fig. 4] d); thus, biopsies of the oral side of the lesion in the rectum were performed to confirm a negative margin. The biopsy scar was difficult to observe macroscopically. Therefore, we performed TaECS to ensure negative resection margins. The defect was repaired using bilateral V-Y advancement flaps. Procedure time was 469 minutes (ESD: 61 minutes; radical vulvectomy and reconstruction: 408 minutes). A postsurgical abscess around the anastomosis in the vaginal area was observed, requiring IV antimicrobial therapy for a month. Histological examination confirmed 50- and 10-mm early-stage vulvar carcinomas without LVI. Lichen sclerosis was mostly observed around the tumor within the resection margins ([Fig. 4] e, [Fig. 4] f, [Fig. 4] g). No additional treatment was applied because all sentinel node biopsies were negative. No recurrence or metastasis was observed at 26-month follow-up.

Fig. 4 Case 3. a Perineal examination showing a reddish 50-mm tumor (red arrowhead) with a 10-mm nodule (yellow arrowhead) and sclerotic and erythematous skin surrounding the lesions. b Endoscopic view of perianal skin showing sclerotic, erythematous skin extending into the anal canal. c Narrow-band imaging showing irregular dilated vessels on erythematous skin. d Endoscopic view revealing no visible lesions in the rectum. e Macroscopic view of specimen after fixation with formalin showing two lesions with sclerotic skin. f Tumor mapping of lesion showing squamous cell carcinoma (SCC) (red line) and lichen sclerosis (green line). g Histological examination confirming SCC diagnosis.

Discussion

We demonstrated that the combination of ESD and LE techniques, collectively referred to as TaECS, enables removal of tumors broadly extending beyond the dentate line.

TaECS has several advantages over other techniques. First, TaECS can preserve the internal anal sphincter by performing a dissection above it. Although APR is a standard treatment for perianal or lower rectal tumors, it would be overkill for non-invasive lesions due to resulting loss of function. Conversely, TaECS can preserve the nerves in the intersphincteric space, thereby preserving anal function postoperatively [5], which is important in maintaining quality of life. Second, TaECS enables precise evaluation of resection margins through endoscopic view. TEM and transanal minimally invasive surgery (TAMIS) can provide precise detection of the extent of lesion distribution. However, TEM and TAMIS cannot be adopted for tumors extending into the anal canal due to scope fixation on the anal canal [3] [6]. Moreover, patients who had undergone initial resection for perianal Paget’s disease had a high positive margin rate of 32% to 42% and required additional resection to attain complete tumor clearance [7]. In contrast, ESD allows precise resection with accurate confirmation of the extent of the lesion. However, tumors that require skin excision cannot be resected by ESD alone. Furthermore, TaECS can accurately dissect the tumor margin using ESD and excise skin beyond the dentate line. Therefore, this combined endoscopic and surgical procedure may ameliorate technical and functional disadvantages of ESD, TAE, TEM, and TAMIS.However, in Case 1, the horizontal margin on the anal side was indeterminate. Coagulation may have occurred during surgical dissection. This can be avoided by securing a wider resection margin.

This case series has some limitations. First, it was a single-center, retrospective study with only three cases. Conclusive evaluation of the feasibility of TaECS requires a prospective multicenter study. However, rarity of the eligible tumors and need for a precise indication for TaECS may limit the number of eligible patients. Previous reports have demonstrated a high incidence of LNM (17%-37%) in cases of invasive extramammary Paget’s disease [8] [9]. Furthermore, APR or chemotherapy was required for recurrent cases [6]. Therefore, the indication for TaECS should be carefully determined via preoperative examination. Second, long-term outcomes after TaECS remain unclear due to the relatively short follow-up period of 17 to 27 months. Although no recurrence was observed, our follow-up period would be insufficient for perianal Paget’s disease and vulvar SCC with lichen sclerosis [4] [7] [10]. Third, TaECS was performed by highly experienced endoscopists and surgeons. For example, ESD for lesions extending into the anal canal is technically difficult [1]. This technical difficulty may be reduced by omitting the submucosal dissection phase and instead making a mucosal incision on the oral side by endoscopy while surgically resecting the remaining area.

Conclusions

In conclusion, TaECS may be a viable treatment for minimally invasive local resection of tumors extending beyond the dentate line.

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