Introduction: Despite advances in endoscopic treatment, patients with serrated polyposis syndrome (SPS) occasionally require surgery due to numerous or unresectable polyps, recurrence, and treatment-related adverse events. Methods: We retrospectively evaluated 43 patients with SPS undergoing diagnosis and treatment at Omori Red Cross Hospital from 2011 to 2022. Resection of all polyps ≥3 mm in size was planned during the clearing phase; endoscopic control was defined as complete, endoscopic polyp removal. During the surveillance phase, patients underwent annual colonoscopy and resection of newly detected polyps ≥3 mm in size. Results: Thirty-eight patients (88%) achieved endoscopic control, two (5%) required surgery after endoscopic treatment because of colorectal cancer (CRC), and three (7%) have not yet achieved endoscopic control and are planning treatment. Endoscopic control was achieved with a median of four colonoscopies at 8 months. Ten polyps (median value) were resected per patient during the clearing phase. Three polyps ≥50 mm in size, six located in the appendiceal orifice, and seven with severe fibrosis could be resected by endoscopic submucosal dissection (ESD). All patients underwent treatment with a combination of cold snare polypectomy (CSP), endoscopic mucosal resection/hot polypectomy, and/or ESD. No case required surgery due to difficulty with endoscopic treatment. Delayed bleeding was observed in 2 cases (0.3%). Twenty-one patients underwent colonoscopies during the surveillance phase. Fifty-three polyps were resected using CSP; no CRC, sessile serrated lesions with dysplasia, or advanced adenoma were detected. Conclusion: SPS can be effectively, efficiently, and safely controlled with appropriate endoscopic management.

Serrated polyposis syndrome (SPS) is characterized by the presence of large and/or multiple serrated lesions (SLs) throughout the colorectum and is associated with a high risk of colorectal cancer (CRC) [1‒3]. Due to this increased risk of CRC, patients with SPS require total management – accurate diagnosis, appropriate treatment, and surveillance. In recent years, several studies revealed new clinicopathological features of SPS [1‒13], and the diagnostic criteria have been revised [14].

Guidelines and several studies have recommended the resection of all polyps ≥3–5 mm and surveillance colonoscopies every 1 to 3 years [1, 2, 15‒17]. Although endoscopic polyp resection is now unarguably the first line of treatment, colorectal surgery is mainly considered if endoscopic control (EC) is infeasible. Patients with SPS undergo colorectal surgery due to the presence of CRC, high polyp burden (number of polyps), unresectable polyps (such as large polyps, polyps located in the appendiceal orifice, and polyps with severe fibrosis), incomplete endoscopic resection, residual recurrence after endoscopic resection, and adverse events of endoscopic treatment. However, the indications for surgery have not been fully established, except for CRC [1, 2, 4‒7].

Whether SPS can be controlled endoscopically depends on the technique and policies of the institution, as well as the patient’s tolerance. Although colorectal resection is relatively safe, it is preferable for patients to avoid surgery if possible. We believe that almost all patients, except those with CRC, can control their disease endoscopically and that it is important to appropriately combine various endoscopic treatments for multiple polyps; approach difficult-to-resect areas effectively; and avoid incomplete resection, recurrence, and adverse events from treatment. Therefore, the aim of the present study was to assess the effectiveness and safety of endoscopic treatment for patients with SPS.

Patients and Study Design

Among 13,282 subjects who underwent colonoscopy at Omori Red Cross Hospital from April 2011 to February 2022, we included those who met the WHO criteria for SPS. We retrospectively analyzed the electronic medical records of the patients who fulfilled SPS diagnostic criteria defined by the World Health Organization (WHO) in 2019 in their fifth edition of the Classification of Tumors of the Digestive System [14]. The latest criteria for SPS are defined as follows: (I) ≥5 SLs/polyps proximal to the rectum, all ≥5 mm in size, with ≥2 being ≥10 mm in size; (II) ≥20 SLs/polyps of any size distributed throughout the large bowel, with ≥5 being proximal to the rectum. The diagnosis of SPS was based on endoscopic, surgical, and histopathological records. The cumulative lifetime polyp count was used for diagnosis.

Demographic data concerning age, sex, body mass index (BMI), cigarette smoking history, personal history of CRC, and previous colonic surgery were ascertained. Indications for total colonoscopy were classified as fecal immunochemical test (FIT)-based screening, primary colonoscopy screening, referral from other hospitals for polyp resection, symptoms, and others. Patients assessed as inadequate on the Aronchick bowel preparation scale and patients with a history of inflammatory bowel disease were excluded. No statistical analysis was performed because the results are descriptive. The primary outcome of this study was the achievement rate of EC. Additionally, we considered the endoscopic treatment combination used to achieve EC, treatment-related adverse events, and detection of advanced neoplasia (CRC, sessile serrated lesion with dysplasia [SSLD] and advanced adenoma, advanced SL) during the surveillance phase.

Procedure

The bowel preparation method in our hospital was as follows: 10 mL of 0.75% sodium picosulfate hydrate was administered the day before colonoscopy and 2 L of polyethylene glycol electrolyte solution on the morning of the colonoscopy. In all patients, either pethidine (17.5–35 mg) + midazolam (1–5 mg) or funitrazepam (0.2–0.5 mg) was administered for conscious sedation at the beginning of the procedure. Intravenous glucagon or scopolamine was administered to reduce colonic movements. A single-channel endoscope (CF-HQ290ZI, PCF-290ZI, PCF-Q260AZI, PCF-Q260J; Olympus Corporation, Tokyo, Japan) with a transparent attachment at the tip and carbon dioxide insufflation were used.

Treatment Protocol

The protocol was divided into the clearing phase and the surveillance phase. To determine the treatment strategy, the size, location, macroscopic type, the presence/absence of dysplasia, and the difficulty of treatment of all polyps were assessed using magnifying endoscopy at the baseline colonoscopies (first endoscopies performed during the study period). The location of the lesions was defined as follows: the right-side colon comprised the cecum, ascending and transverse colon, while the left-side colon included the descending and sigmoid colon. Endoscopic evaluation and mapping were repeated if necessary. All colonoscopies were performed by experienced endoscopists who had performed a total of >1,000 examinations.

Endoscopic or surgical resection of all polyps >3 mm in size was planned during the clearing phase. Achieving EC was defined as complete all polyps with size of >3 mm removal accomplished by endoscopic treatment alone. The first polyp resection was performed frequently during baseline colonoscopy. Additional clearing colonoscopies were performed every 3–12 months based on the polyp burden when this was not possible during one procedure. This process was repeated until all polyps with size of >3 mm, found using baseline colonoscopy, had been resected. Patients who achieved EC entered the surveillance phase at their next colonoscopies, and subsequent surveillance colonoscopies were scheduled annually, again with complete removal of all polyps ≥3 mm.

The endoscopic treatment methods consisted of cold snare polypectomy (CSP), hot polypectomy (HP), endoscopic mucosal resection (EMR) (including endoscopic piecemeal mucosal resection [EPMR]), and endoscopic mucosal dissection (ESD). In principle, CSP, EMR, and HP were used to resect polyps ≥3 mm and <10 mm in size, EMR and HP for polyps ≥10 mm and <20 mm, and ESD for polyps ≥20 mm. Planned EPMR was not scheduled for large polyps. Polyps with dysplasia were preferentially resected using EMR, HP, and ESD. Polyps located within approximately 12 mm of the appendiceal orifice were defined as lesions in proximity to the appendiceal orifice [18]. Polyps ≥50 mm in size, polyps close to the appendiceal orifice, and polyps with severe fibrosis equivalent to F2 were defined as difficult-to-resect lesions [19]. ESD was planned for the resection of such lesions.

CSP was performed on outpatients. To monitor the development of complications, the patients were hospitalized for 1 day after EMR and HP, or 4 days after ESD, and observed using clinical pathways. Multiple polyps were resected during each endoscopy using a combination of treatments, as needed.

CSP was performed with a disposable snare (Snaremaster-Plus; Olympus Co.). HP and EMR (after injection of saline into the submucosa) were performed using a disposable snare (Snaremaster-Plus or Snaremaster; Olympus Co.) and a VIO 300D high-frequency generator (ERBE, Tübingen, Germany). After the injection of a mixture of 0.4% sodium hyaluronate (MucoUp®; Boston Scientifc Japan, Tokyo, Japan) and epinephrine, ESD was performed using a DualKnife (KD-650L; Olympus Co.) and a VIO 300D high-frequency generator.

CSP, EMR, and HP were performed by the aforementioned, experienced endoscopists. ESD was performed by expert endoscopists with colorectal ESD experience of >100 cases.

Surgery was planned for patients endoscopically diagnosed with CRC. In addition, after endoscopic treatment, the patients who had been histopathologically diagnosed with submucosal invasive CRC and/or the presence of lymphatic invasion and vascular involvement were recommended to undergo surgery according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of CRC [20]. The withdrawal and restart periods of the antithrombotic agents were determined based on the Japan Gastroenterological Endoscopy Society guidelines [21].

Histopathological Assessment

All resected specimens were cut into 2-mm slices and stained with hematoxylin and eosin. Some resected specimens were also stained with desmin, EVG, and D2-40 as needed. Expert gastrointestinal-trained pathologists interpreted the histological type, depth of invasion, the presence/absence of lymphatic invasion and vascular involvement, and the lateral and vertical resection margins. All lesions were diagnosed according to WHO classification of tumors of the digestive system [22], and SL were classified as hyperplastic polyps, sessile serrated lesions (SSLs), SSLsD, traditional serrated adenomas (TSAs), or unclassified serrated adenoma. Advanced adenoma was defined as adenoma ≥10 mm in size, and/or with villous structure, and/or high-grade dysplasia. Advanced SL was defined as SL ≥10 mm in size and/or with dysplasia (including TSA).

Study Flow and Patient Characteristics

Of the 13,282 study subjects, 45 (0.34%) met the diagnostic criteria for SPS and of these, two were excluded because they had a known history of inflammatory bowel disease. However, no subjects were excluded because of inadequate evaluation based on the Aronchick bowel preparation scale. Thus, 43 patients were included in the study (shown in Fig. 1).

Fig. 1.

Study flow. Flow of patients throughout the study period. Forty-five patients with SPS were identified. Two patients were excluded due to IBD. Forty-three patients underwent resection of all polyps ≥3 mm during the clearing phase. Ten patients were treated using CSP and EMR/HP, six by CSP and ESD, 27 with CSP, EMR/HP, and ESD. Thirty-eight patients (88%) achieved EC, two (5%) required additional surgery after ESD due to CRC, and three (7%) have not yet achieved EC and are planning endoscopic treatment. The first surveillance colonoscopy was performed on 21 patients, the second on 6 patients, and the third on 2 patients. All polyps detected during the surveillance phase could be resected by CSP. SPS, serrated polyposis syndrome; IBD, inflammatory bowel disease; EC, endoscopic control; CSP, cold snare polypectomy; EMR/HP, endoscopic mucosal resection/hot polypectomy; ESD, endoscopic submucosal dissection; CRC, colorectal cancer.

Fig. 1.

Study flow. Flow of patients throughout the study period. Forty-five patients with SPS were identified. Two patients were excluded due to IBD. Forty-three patients underwent resection of all polyps ≥3 mm during the clearing phase. Ten patients were treated using CSP and EMR/HP, six by CSP and ESD, 27 with CSP, EMR/HP, and ESD. Thirty-eight patients (88%) achieved EC, two (5%) required additional surgery after ESD due to CRC, and three (7%) have not yet achieved EC and are planning endoscopic treatment. The first surveillance colonoscopy was performed on 21 patients, the second on 6 patients, and the third on 2 patients. All polyps detected during the surveillance phase could be resected by CSP. SPS, serrated polyposis syndrome; IBD, inflammatory bowel disease; EC, endoscopic control; CSP, cold snare polypectomy; EMR/HP, endoscopic mucosal resection/hot polypectomy; ESD, endoscopic submucosal dissection; CRC, colorectal cancer.

Close modal

In total, 37 patients (86%) fulfilled WHO criteria I only, while 6 patients (14%) fulfilled WHO criteria I and II. Two patients (5%) had a history of surgery for CRC prior to entering the study. Ten men (56%) and six women (24%) were obese (BMI ≥25) and 21 patients (49%) had a smoking history. The reasons for the first colonoscopy were as follows: (i) FIT-based screening for 19 patients (45%), (ii) primary colonoscopy screening for 4 patients (9%), (iii) referral from another institution for detailed examination or treatment for 10 patients (23%), (iv) symptomatic for 6 patients (14%), and (v) other reasons for 4 patients (9%) (shown in Table 1).

Table 1.

Characteristics of SPS patients who underwent endoscopic treatment (n = 43)

Age at SPS diagnosis, mean±SD, years 63±11 
Male, n (%) 18 (42) 
BMI, mean±SD, kg/m2 24±5 
Overweight/obesity (BMI ≥25), n (%) 16 (37) 
Smoking history, n (%) 21 (49) 
WHO SPS criteriaa, n (%) 
 I 37 (86) 
 II 0 (0) 
 I + II 6 (14) 
Previous CRC, n (%) 2 (5) 
Previous colonic surgery, n (%) 2 (5) 
Reasons for first colonoscopy, n (%) 
 FIT-based screening 19 (45) 
 Primary colonoscopy screening 4 (9) 
 Referral from other institution 10 (23) 
Symptoms 
 Abdominal pain 2 (5) 
 Bleeding 4 (9) 
 Others 4 (9) 
Age at SPS diagnosis, mean±SD, years 63±11 
Male, n (%) 18 (42) 
BMI, mean±SD, kg/m2 24±5 
Overweight/obesity (BMI ≥25), n (%) 16 (37) 
Smoking history, n (%) 21 (49) 
WHO SPS criteriaa, n (%) 
 I 37 (86) 
 II 0 (0) 
 I + II 6 (14) 
Previous CRC, n (%) 2 (5) 
Previous colonic surgery, n (%) 2 (5) 
Reasons for first colonoscopy, n (%) 
 FIT-based screening 19 (45) 
 Primary colonoscopy screening 4 (9) 
 Referral from other institution 10 (23) 
Symptoms 
 Abdominal pain 2 (5) 
 Bleeding 4 (9) 
 Others 4 (9) 

CRC, colorectal cancer; FIT, fecal immunochemical test.

aWHO SPS criteria: (I) ≥5 SLs/polyps proximal to the rectum, all being ≥5 mm in size, with ≥2 being ≥10 mm in size; (II) ≥20 SLs/polyps of any size distributed throughout the large bowel, with ≥5 being proximal to the rectum.

Clearing Phase

Thirty-eight patients (88%) achieved EC; two (5%) patients who underwent ESD required additional colectomy due to CRC, while three (7%) patients have not yet achieved EC and are planning polyp resection. Median values were as follows: four (range: 1–11; IQR: 3–4) clearing colonoscopies per patient to achieve EC, eight (range: 1–45; IQR: 2–22) months to achieve EC, nine (5–36; IQR: 6–16) polyps resected per patient to achieve EC, 10 (range: 5–40; IQR: 7–18) polyps resected per patient (including 3 patients have not achieved EC) during the clearing phase, and three (range: 1–13; IQR: 2–5) polyps resected per colonoscopy (shown in Table 2).

Table 2.

Treatment summary

Total months of follow-up, per patient, median (range) 45 (3–133) 
Total colonoscopies, n (%) 224 
Total resected polyps, per patient, median (range), n (%) 14 (5–43) 
Total resected SLs, per patient, median (range), n (%) 8 (5–29) 
Achieve ECa, n (%) 38 (88) 
Clearing colonoscopies to achieve EC, per patient, median (range), n (%) 4 (1–11) 
Total months of achieving EC, median (range) 8 (1–45) 
Polyps resected to achieve EC, per patient, median (range), n (%) 9 (5–36) 
Total months of surveillance, per patient, median (range) 40 (15–132) 
Surveillance colonoscopies, per patient, median (range), n (%) 1 (1–3) 
Patients with CRC (including prior CRC), n (%) 4 (9) 
TNM staging, n 
 Stage I (T1 N0 M0) 
 Stage IIA (T3 N0 M0) 
 Unknown 
Patients with advanced SLb, n (%) 43 (100) 
Patients with SSLD, n (%) 12 (28) 
Patients with adenoma, n (%) 35 (81) 
Patients with advanced adenomac, n (%) 20 (47) 
Total months of follow-up, per patient, median (range) 45 (3–133) 
Total colonoscopies, n (%) 224 
Total resected polyps, per patient, median (range), n (%) 14 (5–43) 
Total resected SLs, per patient, median (range), n (%) 8 (5–29) 
Achieve ECa, n (%) 38 (88) 
Clearing colonoscopies to achieve EC, per patient, median (range), n (%) 4 (1–11) 
Total months of achieving EC, median (range) 8 (1–45) 
Polyps resected to achieve EC, per patient, median (range), n (%) 9 (5–36) 
Total months of surveillance, per patient, median (range) 40 (15–132) 
Surveillance colonoscopies, per patient, median (range), n (%) 1 (1–3) 
Patients with CRC (including prior CRC), n (%) 4 (9) 
TNM staging, n 
 Stage I (T1 N0 M0) 
 Stage IIA (T3 N0 M0) 
 Unknown 
Patients with advanced SLb, n (%) 43 (100) 
Patients with SSLD, n (%) 12 (28) 
Patients with adenoma, n (%) 35 (81) 
Patients with advanced adenomac, n (%) 20 (47) 

CRC, colorectal cancer; SSLD, sessile serrated lesion with dysplasia.

aEC: complete polyp removal (all polyps ≥3 mm) accomplished by endoscopic treatment alone.

bAdvanced SL: SL with dysplasia, diameter ≥10 mm or TSA.

cAdvanced adenoma: adenoma ≥10 mm in diameter and/or with villous structure and/or high-grade dysplasia.

A total of 638 polyps were resected during the clearing phase, including 413 (64.8%) SLs, 221 (34.6%) adenomas, two (0.3%) CRCs, and two (0.3%) inflammatory polyps. Detailed polyp characteristics are shown in Table 3. Among SLs, there were 272 (42.7%) SSL, 104 (16.3%) hyperplastic polyps, 16 (2.5%) TSA, 16 (2.5%) SSLD, and five (0.8%) unclassified serrated adenoma. Forty-two (6.6%) polyps were advanced adenomas (including 14 [2.2%] adenomas with high-grade dysplasia), and 201 (31.5%) were advanced SL. The median polyp size was 7 mm (range: 3–65; IQR: 5–12).

Table 3.

Statistics of resected lesions

Clearing phaseSurveillance phase
Total resected polyps, n (%) 638 53 
Resected polyps, per patient, median (range), n (%) 10 (5–40) 3 (1–7) 
Size of polyps, median (range), mm 7 (3–65) 5 (3–15) 
Location, n (%) 
 Right-side colona 441 (69) 39 (74) 
 Left-side colonb 163 (26) 8 (15) 
 Rectum 34 (5) 6 (11) 
Histology, n (%) 
 Hyperplastic polyp 104 (16.3) 15 (28.3) 
 SSL 272 (42.7) 8 (15.1) 
 TSA 16 (2.5) 0 (0) 
 SSL with dysplasia 16 (2.5) 0 (0) 
 Unclassified SA 5 (0.8) 0 (0) 
 Adenoma 221 (34.6) 30 (56.6) 
 CRC (T1) 2 (0.3) 0 (0) 
 Inflammatory polyp 2 (0.3) 0 (0) 
Advanced SLc 201 (31.5) 2 (3.8) 
Advanced adenomad 42 (6.6) 0 (0) 
Polyps ≥50 mm in diameter, n (%) 3 (0.5) 0 (0) 
Polyps located in the appendiceal orifice, n (%) 6 (1.0) 0 (0) 
Polyps with severe fibrosis, n (%) 7 (1.1) 0 (0) 
Treatment methods, n (%) 
 CSP 385 (60.4) 53 (100) 
 EMR/HP 155 (24.3) 0 (0) 
 ESD 96 (15.0) 0 (0) 
 Additional surgery after ESD 2 (0.3) 0 (0) 
Adverse events, n (%) 
 Bleeding 2 (0.3) 0 (0) 
 Perforation 0 (0) 0 (0) 
Clearing phaseSurveillance phase
Total resected polyps, n (%) 638 53 
Resected polyps, per patient, median (range), n (%) 10 (5–40) 3 (1–7) 
Size of polyps, median (range), mm 7 (3–65) 5 (3–15) 
Location, n (%) 
 Right-side colona 441 (69) 39 (74) 
 Left-side colonb 163 (26) 8 (15) 
 Rectum 34 (5) 6 (11) 
Histology, n (%) 
 Hyperplastic polyp 104 (16.3) 15 (28.3) 
 SSL 272 (42.7) 8 (15.1) 
 TSA 16 (2.5) 0 (0) 
 SSL with dysplasia 16 (2.5) 0 (0) 
 Unclassified SA 5 (0.8) 0 (0) 
 Adenoma 221 (34.6) 30 (56.6) 
 CRC (T1) 2 (0.3) 0 (0) 
 Inflammatory polyp 2 (0.3) 0 (0) 
Advanced SLc 201 (31.5) 2 (3.8) 
Advanced adenomad 42 (6.6) 0 (0) 
Polyps ≥50 mm in diameter, n (%) 3 (0.5) 0 (0) 
Polyps located in the appendiceal orifice, n (%) 6 (1.0) 0 (0) 
Polyps with severe fibrosis, n (%) 7 (1.1) 0 (0) 
Treatment methods, n (%) 
 CSP 385 (60.4) 53 (100) 
 EMR/HP 155 (24.3) 0 (0) 
 ESD 96 (15.0) 0 (0) 
 Additional surgery after ESD 2 (0.3) 0 (0) 
Adverse events, n (%) 
 Bleeding 2 (0.3) 0 (0) 
 Perforation 0 (0) 0 (0) 

Unclassified SA, unclassified serrated adenoma.

aRight-side colon: cecum, ascending and transverse colon.

bLeft-side colon: descending and sigmoid colon.

cAdvanced SL: SL with dysplasia, diameter ≥10 mm, or TSA.

dAdvanced adenoma: adenoma ≥10 mm in diameter and/or with villous structure and/or high-grade dysplasia.

A total of 385 (60.4%) polyps were resected using CSP, 155 (24.3%) were resected using EMR/HP (including four that were unavoidably resected using EPMR), 96 (15.0%) were resected using ESD, and two (0.3%, CRC) were surgically resected after ESD. There were three polyps (0.5%) ≥ 50 mm in size, six polyps (1.0%) located close to the appendiceal orifice, and seven polyps (1.1%) with fibrosis equivalent to F2, all of which could be resected by ESD (shown in Table 3; Fig. 2).

Fig. 2.

Lesion close to the appendiceal orifice. a Flat lesion 21 mm in size present at the appendiceal orifice, entering deeply into the orifice so that the edges of the lesion cannot be observed. b Magnifying chromoendoscopy with indigo carmine showed type II open-shape pit pattern (type II-O) and villous-like (type IV) pit pattern. c The lesion was resected en bloc using ESD with a loop traction device. d Resected specimen. The lateral margin is free. e Low-power view of tissue section. Histopathological examination reveals SSLD (HE staining, × 4 at objective lens). f Other lesions in the patient. The patient had 12 SSLs and one adenoma; all polyps were resected endoscopically.

Fig. 2.

Lesion close to the appendiceal orifice. a Flat lesion 21 mm in size present at the appendiceal orifice, entering deeply into the orifice so that the edges of the lesion cannot be observed. b Magnifying chromoendoscopy with indigo carmine showed type II open-shape pit pattern (type II-O) and villous-like (type IV) pit pattern. c The lesion was resected en bloc using ESD with a loop traction device. d Resected specimen. The lateral margin is free. e Low-power view of tissue section. Histopathological examination reveals SSLD (HE staining, × 4 at objective lens). f Other lesions in the patient. The patient had 12 SSLs and one adenoma; all polyps were resected endoscopically.

Close modal

The combination of endoscopic treatment methods was as follows: 10 patients (23%) were treated using CSP and EMR/HP, six (14%) by CSP and ESD, 27 (63%) by CSP, EMR/HP, and ESD (shown in Table 4). Delayed bleeding was observed in 2 cases (ESD and HP) (0.3%), but there was no perforation and none of the cases required blood transfusion or emergency surgery.

Table 4.

Combination of endoscopic treatment methods, n (%)

Clearing phase (n = 43)Surveillance phase (n = 19)
CSP and EMR/HP 10 (23) 0 (0) 
CSP and ESDa 6 (14) 0 (0) 
CSP, EMR/HP, and ESDb 27 (63) 0 (0) 
CSP 0 (0) 19 (100) 
Clearing phase (n = 43)Surveillance phase (n = 19)
CSP and EMR/HP 10 (23) 0 (0) 
CSP and ESDa 6 (14) 0 (0) 
CSP, EMR/HP, and ESDb 27 (63) 0 (0) 
CSP 0 (0) 19 (100) 

CSP, cold snare polypectomy; EMR/HP, endoscopic mucosal resection/hot polypectomy; ESD, endoscopic submucosal dissection.

a, b Including 1 patient who underwent surgery after ESD, respectively.

Surveillance Phase

Of 38 patients who achieved EC, 21 patients (55%) underwent surveillance colonoscopies. The median surveillance period per patient was 40 months (range: 15–132, IQR: 33–63), whereas the median number of surveillance colonoscopies per patient was one (range: 1–3, IQR: 1-2). The remaining 17 patients (45%) have not yet undergone initial surveillance colonoscopy (shown in Table 2).

Nineteen patients underwent polyp resection and the median number of resected polyps was three (range: 1–7; IQR: 1–4) per patient. A total of 53 polyps were resected during the surveillance phase, including eight (15.1%) SSL, 15 (28.3%) hyperplastic polyps, and 30 (56.6%) adenomas. Two polyps (3.8%) were advanced SL. No CRCs, SSLD, or advanced adenomas were detected. The median tumor size was 5 mm (range: 3–15; IQR: 3–6) (shown in Table 3). All polyps could be resected using CSP. Adverse events and recurrence were absent.

Throughout the Study Period

The median follow-up duration throughout the study period was 45 (range: 3–133; IQR: 31–71) months. A total of 224 colonoscopies were performed, and 691 polyps were resected by various endoscopic treatment methods. The median number of polyps and SLs resected per patient was 14 (range: 5–43; IQR: 8–21) and eight (range: 5–29, IQR: 6–11), respectively (shown in Tables 2-4). Of the 43 patients, four (9%) had CRC (including 2 patients with prior CRCs), 12 (28%) had SSLD, 43 (100%) had advanced SL, 35 (81%) had adenomas, and 20 (47%) had advanced adenomas.

There were 4 CRC lesions. Two CRCs were resected surgically before SPS diagnosis, whereas the other two were resected using ESD during the clearing phase and required additional surgery. Based on UICC TNM staging, there were two stage I (T1 N0 M0) lesions (resected surgically after ESD), one stage IIA (T3 N0 M0) lesion (resected surgically before SPS diagnosis), and one lesion of an unknown stage (resected surgically at another institution before SPS diagnosis). The histology of CRCs was as follows: two lesions were well-differentiated adenocarcinomas (resected surgically after ESD), one surgically resected lesion was a moderately-to-poorly differentiated mucinous adenocarcinoma, and another one was unknown type. The results of each endoscopic procedure were as follows: 438 polyps with a median size of 5 mm (range: 3–18; IQR: 4–7) were resected using CSP; 155 polyps with a median size of 10 mm (range: 3–30; IQR: 7–14) were resected using EMR/HP; 98 polyps with a median size of 20 mm (range: 6–65; IQR: 17–25) were resected using ESD.

Knowledge of SPS epidemiology, genetic background, pathogenesis, and surveillance has improved in recent years. The patients involved in this study had a mean age of 63 years, and the ratio of males (42%) to females was not significantly different, which is consistent with previous reports [1‒9, 13]. However, most patients (86%) only met criterion I of the WHO 2019 guidelines (≥5 SLs/polyps proximal to the rectum, all ≥5 mm in size, with ≥2 being ≥10 mm in size), which is higher than in Western countries. Additionally, according to the 2019 statistics from the Japanese Ministry of Health, Labour and Welfare [23], when compared with the general population, the patients included in this study had a higher smoking rate (21%) and the males were more obese with BMI ≥25 (56%). Obesity and smoking are associated with a higher risk of SLs [2, 24, 25], which is also indicated by our findings.

One current problem in the treatment of SPS is that there is no unified view regarding the standard for cases for which endoscopic treatment is to be abandoned. The EC achievement rate in several recent studies ranged from 73 to 82% [1, 2, 5‒7]. In the above studies, 8.7–27% of the patients with SPS required colorectal surgery, and of these, 5.2–22.7% of the patients underwent surgery despite the absence of CRC for the following reasons [1, 2, 4‒7]. First, the polyp burden: it is difficult to endoscopically resect all polyps in patients with too many polyps. A total of 0.9 to 10.3% of the patients underwent surgery due to their polyp burden; some patients had been reported to have more than 100 polyps. Second, endoscopically unresectable polyps: 1.3–9.1% of the patients underwent surgery due to unresectable polyps. Large polyps or polyps in the appendiceal orifice or recurrent polyps were reported as reasons for being “unresectable.” Other reasons included perforation caused by polypectomy and tortuosity of the colon. Thus, patient intolerance to repeated colonoscopies, lack of advanced techniques in resecting difficult-to-resect lesions, and recurrence or adverse events may prevent the achievement of EC.

In contrast, 88% of the patients achieved EC in our study. In addition, 3 patients (7%) are in the clearing phase and are expected to achieve EC in the future with continued endoscopic treatment. Our high EC achievement is attributable to the use of advanced techniques and the appropriate combination of various endoscopic methods, which by themselves achieved curative resection for all lesions, except CRC. All patients were treated with a combination of CSP, EMR/HP, and/or ESD. We observed positive results with CSP for smaller lesions without dysplasia. Several studies have shown that CSP is superior to EMR/HP in terms of the procedure time [26, 27], is associated with less delayed bleeding than EMR/HP [28‒31], and can be safely performed in patients using antithrombotic agents [32]. Moreover, all endoscopically resectable polyps with dysplasia were accurately diagnosed and completely treated during the clearing phase. Lesions with dysplasia should be resected using EMR/HP or ESD rather than by CSP because they require an accurate pathological evaluation by en bloc resection. Planned EPMR was not performed to avoid inadequate pathological evaluation and recurrence. Appropriate selection of the treatment method according to the size, atypia, and lesion site contributed to achieving EC with relatively fewer colonoscopies and duration (median of 4 times and 8 months), while maintaining the patient’s tolerance. Furthermore, with advanced ESD techniques [33‒36], three large polyps ≥50 mm in size, six polyps located close to the appendiceal orifice, and seven polyps with severe fibrosis could be resected endoscopically.

On the other hand, the following factors may have favorably influenced our high EC rates. First, the proportion of CRC patients, which is estimated to range from 7.6% to 36.7% [1‒9, 13], was relatively low (9%) in this study cohort, even when including prior CRC cases. Second, because of the higher rate of patients (86%) who only met criterion I of the WHO 2019 guidelines, the median total number of polyps resected per patient during the clearing phase was 10 (range: 5–40, IQR: 7–18), which is lower than reported by other studies [1‒6, 8, 13]. Therefore, no patients required surgery for high polyp burden. The factors contributing to differences in the proportion of CRC and total numbers of polyps between the Western studies and our study are unclear. However, a Korean study have reported a 10% proportion of CRCs [13] and another Japanese study have reported 83% of patients only met criterion I [9], suggesting that genetic differences may be relevant. Third, previous reports, including those from about a decade ago, indicate that ESD was not routinely done in the countries where those studies were conducted and that surgery may have been performed instead.

A total of two advanced SLs were found in 2 patients during the surveillance phase (median duration of 40 months), but no recurrence, CRCs, or advanced adenomas were detected, and all detected lesions could be resected with CSP. The 2 patients with advanced SLs underwent surveillance colonoscopy 13 and 17 months after their last colonoscopy. The respective lesions were a 15 mm SSL without dysplasia located in the ascending colon and a 10 mm SSL without dysplasia located in the transverse colon. Considering the short surveillance period, it was suggested that the lesions were missed polyps rather than newly appearing lesions.

Because evidence from longer surveillance periods was unavailable at the start of our study, we planned annual colonoscopy follow-ups. However, several recent studies have reported extended surveillance periods. The 2015 American College of Gastroenterology guidelines recommend the removal of all polyps with size of ≥5 mm, followed by surveillance colonoscopy at one- to 3-year intervals [15]. A 2017 position paper published by the British Society of Gastroenterology recommends shorter surveillance periods of one or 2 years [16]. The most recent guidelines by the European Society of Gastrointestinal Endoscopy recommend that after removing all polyps with size of ≥5 mm, as well as all polyps (of any size) with suspected dysplasia, surveillance colonoscopy should be performed based on findings of the last colonoscopy [17]. A surveillance interval of 1 year is recommended after the resection of ≥1 advanced polyp or ≥5 non-advanced clinically relevant polyps. In any other situation, a surveillance interval of 2 years is advised. Therefore, we are considering extending our surveillance interval. However, because SLs are flat elevated lesions that are often inconspicuous in color, even relatively large lesions, such as the cases described above, may be missed during the clearing phase. Such lesions may advance into dysplasia or CRC during long surveillance intervals.

There were 2 cases (0.3%) of delayed bleeding but no adverse events requiring blood transfusion or surgery. In addition, no recurrent lesions were found during the study period. These results indicate that complications were minimal and that disease control was good after achieving EC.

This study does have some limitations: (1) It is a single-center, retrospective study. (2) The low number of patients with CRC was thought to have influenced the high EC achievement rate. Since we analyzed endoscopically diagnosed and treated SPS cases, it is possible that some patients with CRC who had undergone surgery or chemotherapy had SPS but could not be diagnosed. Therefore, it is desirable to increase endoscopists’ awareness of the disease concept and diagnostic criteria for SPS. (3) Because there were fewer patients with massive polyp burden, it was easier to achieve EC with a relatively low number of endoscopic procedures and a short duration. (4) We have been actively performing ESD on difficult-to-treat lesions, with good results. However, techniques differ across institutions and countries, and our treatment methods may not be easily adopted by all institutions. (5) Of 38 patients who achieved EC, 17 patients have not yet undergone initial surveillance colonoscopy. Therefore, the possibility that these patients have CRC, advanced adenoma, or advanced SL cannot be ruled out. However, most patients have undergone multiple colonoscopies during the clearing phase, and it is unlikely that such missed lesions are present.

In conclusion, although the number of CRCs and polyps observed in our study differs from those reported in previous studies, we have shown that SPS patients with high polyp burdens, large polyps, polyps in difficult-to-resect areas, and severely fibrotic polyps can be effectively, efficiently, and safely managed through endoscopy. In addition, the low incidence of CRC during the surveillance phase suggests that the preservation of the intestinal tract is safe and significant. Appropriate diagnosis and endoscopic treatment can help avoid surgery.

The research protocol for this study follows the provisions of the Declaration of Helsinki and was approved by Ethics Committee of Omori Red Cross Hospital (the decision reference number 20–23) and registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000050303. All patients were informed and provided written informed consent.

The authors have no conflicts of interest to declare.

The authors have no conflicts of interest to declare.

M.N. and H.C. conceived the study. M.N., H.C., M.K., N.O., J.T., J.A., K.A., and H.K. collected the data and performed colonoscopy and endoscopic treatment. Interpretation of the data was conducted by M.N. and H.C. M.N. wrote the manuscript. All the authors have read the final manuscript and approve of its submission for publication.

All data used in this study are available in the main text. The raw data that support the findings of this study are available from the corresponding author upon reasonable request. Further inquiries can be directed to the corresponding author.

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