Skip Navigation
Skip to contents

Clin Endosc : Clinical Endoscopy

Search
Advanced Search
OPEN ACCESS
mobile search button mobile menu button

Articles

Page Path
HOME > Clin Endosc > Volume 58(6); 2025 > Article
Original Article Long-term outcome of grade 1 rectal neuroendocrine tumor ≤1 cm after incomplete endoscopic resection
Jong Sun Park1orcid, Hye Lynn Jeon2orcid, Bumhee Park2orcid, Jong Hoon Park1orcid, Gil Ho Lee1orcid, Sun Gyo Lim1orcid, Sung Jae Shin1orcid, Kee Myung Lee1orcid, Choong-Kyun Noh1orcid
Clinical Endoscopy 2025;58(6):871-880.
DOI: https://doi.org/10.5946/ce.2025.043
Published online: July 22, 2025

1Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea

2Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea

Correspondence: Choong-Kyun Noh Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea E-mail: cknoh23@gmail.com
• Received: February 7, 2025   • Revised: March 13, 2025   • Accepted: March 15, 2025

© 2025 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 2,476 Views
  • 203 Download
  • 1 Web of Science
  • 1 Crossref
  • 1 Scopus
prev next
Full Article

Download PDF Download PDF

  • Background/Aims
    Surveillance strategies for small grade 1 rectal neuroendocrine tumors (G1 rNETs) after incomplete endoscopic resection (ER) remain controversial. We evaluated the long-term outcomes of patients with G1 rNET ≤1 cm after ER who did and did not undergo complete resection.
  • Methods
    We retrospectively evaluated 441 patients with G1 rNETs measuring ≤1 cm after ER between 2011 and 2022. Patients were divided into complete and incomplete resection groups according to histopathological evaluation. Logistic regression analysis identified the risk factors for incomplete resection after ER.
  • Results
    The mean follow-up intervals were 38.6 and 45.7 months in all patients and the incomplete resection group, respectively. No recurrences were observed during the follow-up period. The mean lesion size was 5.5 mm and the complete resection rate was 80.5% (n=355). In the logistic regression analysis, lesion size 5.1 to 10 mm (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.245–4.203; p=0.008), multiple lesions (OR, 8.3; 95% CI, 1.247–54.774; p=0.029), and retroflexion view during the procedure (OR, 4.0; 95% CI, 1.668–9.615; p=0.002) were independent risk factors for incomplete resection.
  • Conclusions
    The prognosis of G1 rNET ≤1 cm after ER was very good, regardless of the histopathological results.
  • Keywords: Endoscopic resection; Incomplete resection; Neuroendocrine tumors; Recurrence; Rectum
Rectal neuroendocrine tumors (rNETs) have been increasingly diagnosed for many years because of increased colonoscopy screening, and their incidence has increased approximately 10-fold over the past 30 years.1-3 Small rNETs (<10 mm) with no lymphovascular invasion (LVI) can be confused with hyperplastic polyps or adenomas.4 However, even among LVI-positive cases, no distinct endoscopic features have been identified to reliably differentiate them from LVI-negative cases. Therefore, these lesions are occasionally removed by snare polypectomy or even cold biopsy rather than by other endoscopic resection (ER) modalities, including modified endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and surgical resection, such as transanal minimally invasive surgery (TAMIS).5 This can lead to incomplete resection of rNETs,4 causing uncertainty and anxiety regarding the follow-up strategy for both endoscopists and patients. Therefore, it is necessary to determine the best way to manage such cases.
Although grade 1 (G1) rNETs are slow-growing tumors with an extremely low rate of metastasis,6 whether additional ER or surgical resection is necessary in patients with incomplete resection remains controversial. Recent European Neuroendocrine Tumor Society guidelines recommend that for G1 rNETs without LVI, if the lesion is <10 mm with incomplete resection and imaging studies show no abnormalities, the patient may choose ER, TAMIS, or surveillance.7 In contrast, endoscopic full-thickness resection or TAMIS is recommended for 10–20 mm lesions with R1 resection.7 This suggests that positive resection margins, whether vertical or lateral, do not always indicate a remnant tumor at the resection site. However, endoscopists have difficulty deciding whether to perform further endoscopic treatments. While the European Neuroendocrine Tumor Society 2023 guidelines primarily recommend salvage treatment for all R1-resected patients, they suggest that in selected low-risk cases (G1L0V0) with significant comorbidities, a surveillance approach should be considered after thorough patient consultation and careful long-term follow-up. Furthermore, limited long-term data on surveillance outcomes after incomplete resection creates uncertainty in clinical decision-making. Therefore, real-world studies with long-term follow-up are required to provide additional guidance to clinicians.
To provide guidance, we investigated whether a watch-and-wait strategy is appropriate for patients with confirmed small G1 rNET after ER with incomplete resection. This study aimed to evaluate the long-term outcomes of patients with G1 rNET ≤1 cm after ER, regardless of the histopathological results, including margin positivity and LVI. To the best of our knowledge, this study had the longest follow-up duration among studies examining this question.
Patients
We retrospectively reviewed the data of patients diagnosed with G1 rNET measuring ≤1 cm after ER at the Ajou University Hospital (Suwon) between January 2011 and December 2022. The exclusion criteria were as follows: (1) indeterminate margins on histopathological evaluation, (2) total follow-up of less than 12 months, and (3) incomplete resection and additional treatment after ER.
rNET work-up and ER
For patients with rNET confirmed after ER at a local clinic or at our center, excised specimen slides were sent to our center’s expert pathologist for histopathological evaluation. For patients with suspected subepithelial tumors who were referred to our center for removal, endoscopic ultrasonography (EUS; GF-UC240P-AL5; Olympus Optical Co.) was performed to evaluate the tumor depth before ER. The tumors were removed via conventional EMR using a snare, EMR using the strip biopsy method (EMR-S),8-10 EMR after circumferential precutting (EMR-P), or ESD. EMR-S, a modified EMR technique, was performed using a two-channel endoscope (GIF-2TQ260M; Olympus Optical Co.). After injecting hypertonic saline and diluted epinephrine solution mixed with indigo carmine dye into the submucosa to elevate the lesion, alligator forceps were introduced through one channel of the endoscope to grasp and lift the lesion. A polypectomy snare was inserted through the second channel and positioned below the grasping forceps to capture the submucosal layer. Once the lesion was securely grasped, the snare was closed and electrocautery was applied to achieve en bloc resection. This technique facilitates deeper submucosal capture, allowing for a more complete resection and minimizing the risk of incomplete excision.9,10 EMR-P was performed using a snare tip to make a circumferential incision, followed by removal of the lesion with a snare. ESD was performed by using a needle-type knife (Dual Knife, KD-650; Olympus Optical Co.). All procedures were performed by expert endoscopists with experience in >500 gastric ESD procedures.
Histopathological evaluation
All specimens were examined by expert pathologists at our center to determine tumor size, depth, resection margin status (lateral and vertical), and LVI. The mitotic count and Ki-67 index were additionally assessed to measure tumor grade according to the World Health Organization grading system.11
Follow-up after ER
Follow-up endoscopy was performed 3 months after ER and annually thereafter. At all follow-up visits, three or four biopsy samples were obtained from the ER sites, regardless of whether the patients underwent complete resection. Recurrence at sites other than the ER was also assessed, and a biopsy was performed at the discretion of the endoscopist. Computed tomography (CT) was performed during the initial work-up and annually thereafter to check for lymph node or distant metastases. EUS was performed at each follow-up visit in patients with incomplete resection.
Study outcomes and definitions
The primary outcome was recurrence after ER in the patients with G1 rNET ≤1cm. We also compared the clinical characteristics (baseline characteristics and clinical outcomes) of the complete and incomplete resection groups and investigated the risk factors for incomplete resection after ER.
Complete resection was defined as negative resection margins (both horizontal and vertical) and absence of LVI. Local recurrence was defined as the diagnosis of NET at the resection site on pathological evaluation. Distant recurrence was defined as the detection of a new lesion on follow-up endoscopy or CT scans.
Statistical analyses
Data are presented as numbers and percentages for categorical variables and as means and standard deviations (SDs) for continuous variables. Differences between the complete and incomplete resection groups were compared using the t-test or analysis of variance for continuous variables and the chi-square test for categorical variables. Logistic regression models were used to evaluate risk factors associated with incomplete resection after ER. Statistical analyses were performed using the R software ver. 4.3.1 (R Project for Statistical Computing). All statistical analyses were two-sided, and p-values <0.05 were considered statistically significant.
Ethical statements
The study protocol was approved by the Institutional Review Board and Ethics Committee of Ajou University Hospital (approval number: AJOUIRB-DB-2024-117). The requirement for written informed consent was waived due to the retrospective nature of this study.
Study population and baseline characteristics
In total, 441 patients who underwent ER for rNETs were enrolled in our study (Fig. 1); 60.8% (n=268) were male, and the mean was 46.7±11.7 years. The mean size was 5.5±1.8 mm in work-up endoscopy before ER, and all lesions were ≤10 mm. Six (1.4%) patients had multiple lesions. We performed EUS before tumor removal in 327 patients (74.1%) and we observed no involvement of the muscularis propria except one indeterminate case. All lesions were removed using endoscopic methods, with EMR-S (n=330, 74.8%) being the most commonly used method. When approaching the tumor was difficult or the tumor was close to the anus, endoscopists performed the procedure using a retroflexion view, which occurred in 9.3% (n=41) of cases. The complete resection rate was 80.5% (n=355). Margin positivity and LVI were observed in 18.1% (n=80) and 2.0% (n=9) of patients with incomplete resection, respectively (Table 1).
Comparison of characteristics and clinical outcomes between the complete and incomplete resection groups
Based on the final histopathological results, we divided the patients into two groups according to whether the lesion was completely resected. Regarding baseline characteristics (Table 2), the lesion size and distribution were significantly different between the two groups. The mean lesion size in the incomplete resection group was larger than that in the complete resection group (complete resection vs. incomplete resection, 5.4±1.7 vs. 6.1±1.8 mm; p<0.001). The overall distribution of the lesion size differed significantly between the complete and incomplete resection groups (p=0.003). In particular, the proportion of patients with 5.1 to 10 mm lesions was lower in the complete resection group than in the incomplete resection group (41.7% vs. 59.3%). A comparison of the clinical outcomes between the two groups is shown in Table 3. In both groups, EMR-S was the most common treatment modality; however, EMR-P and ESD, which remove lesions after circumferential incision, were more common in the incomplete resection group than in the complete resection group (7.9% vs. 14.0%, p=0.009). Among the 441 included patients, 34.2% (n=151) of lesions were located within 5 cm of the anal verge, whereas 65.8% (n=290) were beyond 5 cm. The retroflexion view in the scope position during tumor resection was more common in the incomplete resection group than in the complete resection group (7.3% vs. 17.4%, p=0.004). The tumor size in the final histopathology was larger in the incomplete resection group than in the complete resection group (4.5±1.9 vs. 4.0±1.7 mm, p=0.018). All lesions in both groups had mitotic counts <2/10 high-power fields and Ki-67 indices <2%.
Logistic regression analysis was performed to investigate risk factors associated with incomplete resection after ER (Table 4). In multivariate analysis, lesion size 5.1 to 10 mm (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.245–4.203; p=0.008), multiple lesions (OR, 8.3; 95% CI, 1.247–54.774; p=0.029), and retroflexion view during the procedure (OR, 4.0; 95% CI, 1.668–9.615; p=0.002) were associated with incomplete resection after ER. However, the type of ER technique was not.
Long-term outcomes
The mean follow-up period in all patients was 38.6±26.9 months. The mean follow-up period in the incomplete resection group was longer than that in the complete resection group (45.7±29.1 vs. 36.9±26.1 months, p=0.004). During the follow-up period, no local recurrence or distant metastasis was observed, regardless of whether the patient underwent complete tumor removal. No disease-related mortality was observed in either group.
rNETs generally have a favorable prognosis, with a 5-year survival rate of 88.3% for all stages; however, there is still concern about whether to follow up cases with incompletely resected small G1 rNET or proceed with additional endoscopic or surgical management.4,12 Our study was designed to determine whether G1 rNET ≤1 cm with incomplete resection can be managed with a watch-and-wait strategy without the need for salvage treatment, such as further ER or surgery. To the best of our knowledge, this study had a longer follow-up duration than previous studies that have examined this question. In addition, we identified factors associated with incomplete resection after ER. In our study, a lesion size of 5.1 to 10 mm, multiple lesions, and scope position (retroflexion view) were associated with incomplete resection. However, after the removal of the G1 rNET by ER, no recurrence was observed during the follow-up period, regardless of whether the patient underwent complete resection. Moreover, there were no local or distant recurrences during the follow-up period, even in patients with LVI. Interestingly, the mean follow-up period was longer in the incomplete resection group than in the complete resection group.
Among patients with incomplete resection, 2.2% (n=10) were referred to our center for further evaluation and management after undergoing ER at local clinics. Of the ten patients, nine (2.0%) underwent conventional EMR, and only one (0.2%) underwent cold snare polypectomy (CSP). Among the cases of incomplete resection (R1 resection) in our study, two were resected using conventional EMR, and one using CSP. However, follow-up endoscopic biopsy and imaging of the CSP case revealed no residual disease, and histopathological evaluation by an expert pathologist confirmed the absence of remnant tumor cells.
European and National Comprehensive Cancer Network guidelines exist regarding follow-up treatment after incomplete resection of G1 rNETs, but there are subtle differences between them.7,13 The former recommends at least 5 years of endoscopy and EUS or magnetic resonance imaging (MRI) annually if a second ER or TAMIS is not performed to achieve R0 status.7 The latter proposes a 6–12-month follow-up for incompletely resected G1 rNETs ≤10 mm in diameter; if there is no confirmation of a residual lesion, no further follow-up is recommended.13 Controversy exists upon these slight differences for NETs with incomplete resection, thereby producing concerns for both endoscopist and patient. Starting in January 2021, the Korean Standard Classification of Diseases-8 removed the classification of carcinoid tumors of uncertain malignant potential, and the behavioral code was changed.14 Consequently, all rNETs, regardless of tumor grade, are now uniformly considered to have malignant potential. This could lead to anxiety if the endoscopist adopts a watch-and-wait strategy rather than additional treatment. Our study suggests that surveillance without additional ER or surgical modalities is possible and can, therefore, alleviate such concerns and establish an endoscopist treatment consensus regarding incompletely resected small G1 rNETs.
rNETs are highly vascular; therefore, LVI is a significant risk factor for metastasis.15 Tumor size >5 mm is a risk factor for LVI in small rNETs.16 However, tumor grade does not increase the risk of LVI.16 The LVI status in endoscopically resected specimens is also a risk factor for subsequent lymph node metastasis.16 Therefore, patients with G1 rNETs with LVI should be carefully examined to rule out the risk of metastasis. However, there is no consensus on whether to proceed with additional treatment modalities or surveillance of rNETs with LVI. Notably, no distinct endoscopic features were observed in these LVI-positive cases that could reliably differentiate them from LVI-negative cases. Given that LVI is a histopathological characteristic rather than a macroscopic finding, expert pathologist evaluation is essential for an accurate assessment. In our study, LVI was observed in nine lesions across nine patients, with a mean follow-up period of 38.1 months and a mean lesion size of 5.9 mm. Among these, three lesions had incomplete resection margins. Surgical intervention was initially considered for three patients in our study, and two additional patients were referred to surgeons for further evaluation. However, after multidisciplinary discussions, the oncological benefit of surgery was considered minimal relative to the surgical risks, particularly given the small tumor size and low proliferative index (G1). Additionally, two patients declined surgery due to concerns regarding postoperative complications, particularly low anterior resection syndrome. Given these factors, tumor characteristics, patient preferences, and oncological risk assessments play crucial roles in decision-making. Consequently, all LVI (+) patients were managed with surveillance, and no recurrence was observed during the mean follow-up period of 38.1 months. CT was performed to evaluate recurrence after ER; however, none of the patients had local or distant metastases to solid organs or lymph node involvement. Therefore, our findings suggest that endoscopically resected small G1 rNETs with LVI can be carefully followed up for approximately 4 years without needing salvage therapy. However, considering that the LVI (+) status is a well-established risk factor for lymph node metastasis, further studies with extended follow-up and larger cohorts are necessary to verify the long-term oncological safety of this surveillance approach. Prospective multicenter trials could help establish more definitive guidelines for managing LVI (+) G1 rNETs after ER. A literature review revealed two reported cases of positive LVI with disease recurrence: one for a 20 mm tumor that recurred after 18 months, and the other that presented with distant metastasis at diagnosis. Sufficient data are required to clarify the guidelines and recommendations for LVI status in treatment decisions.17,18
In clinical practice, rectal retroflexion is considered an essential part of a complete colonoscopy.19 A low rate of major complications, including bleeding, perforation, and possible detection of undetectable lesions by forward view, may assist in maneuvering the retroflexion view at the rectum.20 We found that the retroflexion position during ER increased the risk of incomplete resection by four times compared to the forward view (p=0.002). However, no previous studies have reported such interesting results. The proportion of ERs in the retroflexion view lesions located ≤5 cm was higher than that in the retroflexion view >5 cm (14.6%, n=26 vs. 6.8%, n=20, respectively). The proportion of ERs in the retroflexion view decreased as the lesion location moved proximally; 14.6% (n=22) for lesions located within 5 cm of the anal verge, 7.6% (n=19) for lesions between 5 and 10 cm, and none for lesions >10 cm. The frequent use of retroflexion in these cases was primarily influenced by technical considerations, rather than operator preference. Specifically, retroflexion is more commonly required in the EMR-S technique because of the need for optimal lesion grasping and snaring during difficult angulation. In contrast, EMR-L and EMR-P, which provide a more stable lesion capture in the forward view, do not require retroflexion as frequently. These findings suggest that the decision to use retroflexion is mainly determined by both lesion location and the specific requirements of the resection technique, rather than subjective operator preference alone. Further studies are warranted to evaluate the effect of retroflexion across different EMR techniques on resection outcomes and procedural difficulties. In addition, our endoscopist preferred EMR-S, which requires a two-channel endoscope. Modified EMR methods, including EMR-S and EMR-P, are considered better treatment options than conventional EMR for rNETs.9 However, the most important factors for determining which modified EMR method should be employed are the endoscopist’s expertise and preference and the availability of equipment, because no notable differences in outcomes exist between modified treatment methods and conventional EMR.9 During EMR-S, grasping forceps lift the lesion upward while polypectomy snaring is directed toward the downward force to the lesion. This simultaneous opposite maneuver of the vector direction requires highly experienced endoscopists and significant training time, making it difficult to achieve complete resection of G1 rNETs. We speculate that the retroflexion view, rather than the forward view, may increase the complexity of EMR-S, leading to incomplete resection.
Our study had some limitations. First, this was a single-center, retrospective study, which may have introduced a selection bias, thereby limiting the generalizability of our findings. Second, patients with a follow-up period of less than 12 months were excluded from our study in both the complete and incomplete resection groups (n=111 vs. n=13). Third, our experienced endoscopist favored EMR-S over EMR with a ligation device (EMR-L) for ER of small rNETs. Although EMR-L has been reported to achieve a higher complete resection rate than ESD with a much shorter procedure time, this preference has led to a potential selection bias, limiting direct comparisons between modified EMR techniques.21 Fourth, the post-endoscopic imaging surveillance methods adopted by our center, such as abdominal and chest CT, are less capable of detecting minor changes and lymph node metastases than MRI or gallium-68 positron emission tomography/computed tomography (PET/CT). This limitation may have led to an underestimation of the recurrence rates. Future studies should incorporate more advanced imaging techniques to improve the detection of recurrence. Lastly, despite our efforts to analyze potential prognostic factors, we were unable to identify any significant risk factors associated with recurrence because there was no recurrence of events in our study cohort. Larger multicenter studies with extended follow-up periods are necessary to assess the predictive factors for recurrence after ER in rNETs G1.
In conclusion, our study showed that the long-term prognosis of incompletely resected G1 rNET ≤1 cm allows for a watch-and-wait strategy rather than additional endoscopic or surgical resection because metastasis to distant solid organs or lymph nodes was not observed during the mean follow-up period of 45.7 months, which is the longest follow-up period to date. Therefore, if G1 rNETs ≤1 cm are removed endoscopically, the prognosis is very good regardless of the histopathological results, and we expect our results to provide psychological reassurance to both endoscopists and patients during surveillance after ER.
Fig. 1.
Flowchart for the enrollment of the patients. G1 rNET, grade 1 rectal neuroendocrine tumor; ER, endoscopic resection.
ce-2025-043f1.jpg
ce-2025-043f2.jpg
Table 1.
Baseline characteristics and procedure outcomes
Characteristic Total (n=441)
Age (yr) 46.7±11.7
Male 268 (60.8)
Distance from anal verge (cm) 8.0 (5.0–10.0)
Multiple lesions 6 (1.4)
Lesion size (mm) 5.5±1.8
EUS finding (n=327)
 Depth
  Submucosaa) 326 (99.7)
  Indeterminate 1 (0.3)
 Echogenicity (n=324)
  Hypoechoic 304 (93.8)
  Other 20 (6.2)
Treatment method
 Conventional EMRb) 71 (16.1)
 EMR-Sc) 330 (74.8)
 EMR-Pd) 15 (3.4)
 ESD 25 (5.7)
Scope position during resection
 Forward view 400 (90.7)
 Retroflexion view 41 (9.3)
Outcomes
 Complete resection 355 (80.5)
 Non-complete resection 86 (19.5)
  Margin positive 80 (18.1)
  Lymphovascular invasione) 9 (2.0)

Values are presented as mean±standard deviation or number (%).

EUS, endoscopic ultrasonography; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection.

a)Including muscularis mucosa and submucosa;

b)including cold snare polypectomy (n=1);

c)endoscopic mucosal resection with the strip biopsy method;

d)endoscopic mucosal resection after circumferential precutting;

e)In two cases, margin positivity was also confirmed.

Table 2.
Comparison of baseline characteristics between the complete and incomplete resection groups after endoscopic resection for rectal NET
Complete resection (n=355) Incomplete resection (n=86) p-value
Age (yr) 0.106
 <40 115 (32.4) 18 (20.9)
 40–59 182 (51.3) 50 (58.1)
 ≥60 58 (16.3) 18 (20.9)
Male 218 (61.4) 50 (58.1) 0.577
Lesion size (mm) 5.4±1.7 6.1±1.8 <0.001
Lesion size (mm)
 ≤5 207 (58.3) 35 (40.7) 0.003
 5–10 148 (41.7) 51 (59.3)
Distance from anal verge (cm) 7.8±3.2 7.7±2.9 0.782
Multiple lesions 3 (0.8) 3 (3.5) 0.091
EUS finding (n=327)
 Origin 1.000
  Submucosaa) 269 (99.6) 57 (100.0)
  Indeterminate 1 (0.4) 0 (0)
 Echogenicity 0.220
  Hypoechoic 248 (92.9) 56 (98.2)
  Other 19 (7.1) 1 (1.8)

Values are presented as number (%) or mean±standard deviation.

NET, neuroendocrine tumor; EUS, endoscopic ultrasonography.

a)Including muscularis mucosa and submucosa.

Table 3.
Comparison of procedure outcomes between the complete and incomplete resection groups after endoscopic resection for rectal NET
Complete resection (n=355) Incomplete resection (n=86) p-value
Treatment method 0.009
 Conventional EMRa) 50 (14.1) 21 (24.4)
 EMR-Sb) 277 (78.0) 53 (61.6)
 EMR-Pc) 9 (2.5) 6 (7.0)
 ESD 19 (5.4) 6 (7.0)
Scope position during resection 0.004
 Forward view 329 (92.7) 71 (82.6)
 Retroflexion view 26 (7.3) 15 (17.4)
Tumor size (mm) 4.0±1.7 4.5±1.9 0.018
Resection margin status NA
 Negative 0 (0) 6 (7.0)
 Positive 0 (0) 80 (93.0)
  Lateral margin positive 0 (0) 3 (3.8)
  Deep margin positive 0 (0) 75 (93.8)
  Both margin positive 0 (0) 2 (2.5)
Lymphovascular invasion 0 (0) 9 (10.5) NA
Mitotic count <2/10 HPF 355 (100.0) 86 (100.0) 1.000
Ki-67 index 0.909
 <1% 101 (28.5) 25 (29.1)
 1–2% 254 (71.5) 61 (70.9)

Values are presented as number (%) or mean±standard deviation.

NET, neuroendocrine tumor; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; EUS, endoscopic ultrasonography; HPF, high-power fields; NA, not applicable.

a)Including cold snare polypectomy (complete resection, n=9; incomplete resection, n=1);

b)endoscopic mucosal resection with strip biopsy method;

c)endoscopic mucosal resection after circumferential precutting.

Table 4.
Logistic regression analysis for determining factors associated with incomplete resection after endoscopic resection
Variable Univariate
 Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age (yr)
 <40 Ref.
 40–59 1.8 (0.976–3.157) 0.060
 ≥60 2.0 (0.960–4.096) 0.064
Male sex 0.9 (0.541–1.409) 0.578
Lesion size (mm)
 ≤5 Ref. Ref.
 5–10 2.0 (1.262–3.291) 0.004 2.3 (1.245–4.203) 0.008
Multiple lesions 4.2 (0.841–21.389) 0.080 8.3 (1.247–54.774) 0.029
Echogenicity in EUS
 Hypoechoic Ref. Ref.
 Indeterminate 0.2 (0.031–1.778) 0.160 0.2 (0.027–1.656) 0.138
Treatment method
 Conventional EMR Ref. Ref.
 EMR-Sa) 0.5 (0.253–0.820) 0.009
 EMR-Pb) 1.6 (0.502–5.022) 0.432
 ESD 0.8 (0.263–2.148) 0.594
Scope position
 Forward view Ref. Ref.
 Retroflexion view 2.7 (1.347–5.305) 0.005 4.0 (1.668–9.615) 0.002

OR, odds ratio; CI, confidence interval; ref., reference; EUS, endoscopic ultrasonography; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection.

a)Endoscopic mucosal resection with strip biopsy method;

b)endoscopic mucosal resection after circumferential precutting.

  • 1. Gallo C, Rossi RE, Cavalcoli F, et al. Rectal neuroendocrine tumors: current advances in management, treatment, and surveillance. World J Gastroenterol 2022;28:1123–1138.ArticlePubMedPMC
  • 2. Lumsdaine CT, Liu-Smith F, Li X, et al. Increased incidence of early onset colorectal adenocarcinoma is accompanied by an increased incidence of rectal neuroendocrine tumors. Am J Cancer Res 2020;10:1888–1899.PubMedPMC
  • 3. Chablaney S, Zator ZA, Kumta NA. Diagnosis and management of rectal neuroendocrine tumors. Clin Endosc 2017;50:530–536.ArticlePubMedPMCPDF
  • 4. Ma XX, Wang LS, Wang LL, et al. Endoscopic treatment and management of rectal neuroendocrine tumors less than 10 mm in diameter. World J Gastrointest Endosc 2023;15:19–31.ArticlePubMedPMC
  • 5. Basuroy R, Haji A, Ramage JK, et al. Review article: the investigation and management of rectal neuroendocrine tumours. Aliment Pharmacol Ther 2016;44:332–345.ArticlePubMed
  • 6. Jung YS, Yun KE, Chang Y, et al. Risk factors associated with rectal neuroendocrine tumors: a cross-sectional study. Cancer Epidemiol Biomarkers Prev 2014;23:1406–1413.ArticlePubMedPDF
  • 7. Rinke A, Ambrosini V, Dromain C, et al. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours. J Neuroendocrinol 2023;35:e13309.ArticlePubMed
  • 8. Tanabe S, Koizumi W, Mitomi H, et al. Usefulness of EMR with an oblique aspiration mucosectomy device compared with strip biopsy in patients with superficial esophageal cancer. Gastrointest Endosc 2004;59:558–563.ArticlePubMed
  • 9. Lee HS, Moon HS, Kwon IS, et al. Comparison of conventional and modified endoscopic mucosal resection methods for the treatment of rectal neuroendocrine tumors. Surg Endosc 2021;35:6055–6065.ArticlePubMedPDF
  • 10. Hong SM, Baek DH. Endoscopic treatment for rectal neuroendocrine tumor: which method is better? Clin Endosc 2022;55:496–506.ArticlePubMedPMCPDF
  • 11. Rindi G, Petrone G, Inzani F. The 2010 WHO classification of digestive neuroendocrine neoplasms: a critical appraisal four years after its introduction. Endocr Pathol 2014;25:186–192.ArticlePubMedPDF
  • 12. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97:934–959.ArticlePubMed
  • 13. Shah MH, Goldner WS, Benson AB, et al. Neuroendocrine and adrenal tumors, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2021;19:839–868.ArticlePubMed
  • 14. Kim ES. Update of Korean standard classification of diseases for rectal carcinoid and its clinical implication. J Dig Cancer Res 2021;9:57–59.Article
  • 15. Yazdani S, Kasajima A, Tamaki K, et al. Angiogenesis and vascular maturation in neuroendocrine tumors. Hum Pathol 2014;45:866–874.ArticlePubMed
  • 16. Kang HS, Kwon MJ, Kim TH, et al. Lymphovascular invasion as a prognostic value in small rectal neuroendocrine tumor treated by local excision: a systematic review and meta-analysis. Pathol Res Pract 2019;215:152642.ArticlePubMed
  • 17. Shigeta K, Okabayashi K, Hasegawa H, et al. Long-term outcome of patients with locally resected high- and low-risk rectal carcinoid tumors. J Gastrointest Surg 2014;18:768–773.ArticlePubMedPDF
  • 18. Yamagishi D, Matsubara N, Noda M, et al. Clinicopathological characteristics of rectal carcinoid patients undergoing surgical resection. Oncol Lett 2012;4:910–914.ArticlePubMedPMC
  • 19. Hanson JM, Atkin WS, Cunliffe WJ, et al. Rectal retroflexion: an essential part of lower gastrointestinal endoscopic examination. Dis Colon Rectum 2001;44:1706–1708.ArticlePubMed
  • 20. Téllez-Ávila F, Barahona-Garrido J, García-Osogobio S, et al. Diagnostic yield and therapeutic impact of rectal retroflexion: a prospective, single-blind study conducted in three centers. Clin Endosc 2014;47:79–83.ArticlePubMedPMC
  • 21. Bang BW, Park JS, Kim HK, et al. Endoscopic resection for small rectal neuroendocrine tumors: comparison of endoscopic submucosal resection with band ligation and endoscopic submucosal dissection. Gastroenterol Res Pract 2016;2016:6198927.ArticlePubMedPMCPDF

Figure & Data

REFERENCES

    Citations

    Citations to this article as recorded by  
    • Prognostic Factors in Neuroendocrine Neoplasms of the Rectum
      Frederike Butz, Charlotte Friederike Müller-Debus, Flora Georgina Ecseri, Gianna Sophia Mani, Elif Akgündüz, Agata Dukaczewska, Peter Richard Steinhagen, Uli Fehrenbach, Catarina A. Kunze, Henning Jann, Johann Pratschke, Eva Maria Dobrindt, Martina T. Mog
      Cancers.2025; 17(17): 2841.     CrossRef

    • PubReader PubReader
    • ePub LinkePub Link
    • Cite
      CITE
      export Copy Download
      Close
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Long-term outcome of grade 1 rectal neuroendocrine tumor ≤1 cm after incomplete endoscopic resection
      Clin Endosc. 2025;58(6):871-880.   Published online July 22, 2025
      DOI: https://doi.org/10.5946/ce.2025.043
      Close
    • XML DownloadXML Download
    Figure
    • 0
    • 1
    Related articles
    Long-term outcome of grade 1 rectal neuroendocrine tumor ≤1 cm after incomplete endoscopic resection
    Image Image
    Fig. 1. Flowchart for the enrollment of the patients. G1 rNET, grade 1 rectal neuroendocrine tumor; ER, endoscopic resection.
    Graphical abstract

    Fig. 1.

    Graphical abstract

    Long-term outcome of grade 1 rectal neuroendocrine tumor ≤1 cm after incomplete endoscopic resection
    Characteristic Total (n=441)
    Age (yr) 46.7±11.7
    Male 268 (60.8)
    Distance from anal verge (cm) 8.0 (5.0–10.0)
    Multiple lesions 6 (1.4)
    Lesion size (mm) 5.5±1.8
    EUS finding (n=327)
     Depth
      Submucosaa) 326 (99.7)
      Indeterminate 1 (0.3)
     Echogenicity (n=324)
      Hypoechoic 304 (93.8)
      Other 20 (6.2)
    Treatment method
     Conventional EMRb) 71 (16.1)
     EMR-Sc) 330 (74.8)
     EMR-Pd) 15 (3.4)
     ESD 25 (5.7)
    Scope position during resection
     Forward view 400 (90.7)
     Retroflexion view 41 (9.3)
    Outcomes
     Complete resection 355 (80.5)
     Non-complete resection 86 (19.5)
      Margin positive 80 (18.1)
      Lymphovascular invasione) 9 (2.0)
    Complete resection (n=355) Incomplete resection (n=86) p-value
    Age (yr) 0.106
     <40 115 (32.4) 18 (20.9)
     40–59 182 (51.3) 50 (58.1)
     ≥60 58 (16.3) 18 (20.9)
    Male 218 (61.4) 50 (58.1) 0.577
    Lesion size (mm) 5.4±1.7 6.1±1.8 <0.001
    Lesion size (mm)
     ≤5 207 (58.3) 35 (40.7) 0.003
     5–10 148 (41.7) 51 (59.3)
    Distance from anal verge (cm) 7.8±3.2 7.7±2.9 0.782
    Multiple lesions 3 (0.8) 3 (3.5) 0.091
    EUS finding (n=327)
     Origin 1.000
      Submucosaa) 269 (99.6) 57 (100.0)
      Indeterminate 1 (0.4) 0 (0)
     Echogenicity 0.220
      Hypoechoic 248 (92.9) 56 (98.2)
      Other 19 (7.1) 1 (1.8)
    Complete resection (n=355) Incomplete resection (n=86) p-value
    Treatment method 0.009
     Conventional EMRa) 50 (14.1) 21 (24.4)
     EMR-Sb) 277 (78.0) 53 (61.6)
     EMR-Pc) 9 (2.5) 6 (7.0)
     ESD 19 (5.4) 6 (7.0)
    Scope position during resection 0.004
     Forward view 329 (92.7) 71 (82.6)
     Retroflexion view 26 (7.3) 15 (17.4)
    Tumor size (mm) 4.0±1.7 4.5±1.9 0.018
    Resection margin status NA
     Negative 0 (0) 6 (7.0)
     Positive 0 (0) 80 (93.0)
      Lateral margin positive 0 (0) 3 (3.8)
      Deep margin positive 0 (0) 75 (93.8)
      Both margin positive 0 (0) 2 (2.5)
    Lymphovascular invasion 0 (0) 9 (10.5) NA
    Mitotic count <2/10 HPF 355 (100.0) 86 (100.0) 1.000
    Ki-67 index 0.909
     <1% 101 (28.5) 25 (29.1)
     1–2% 254 (71.5) 61 (70.9)
    Variable Univariate
    		 Multivariate
    OR (95% CI) p-value OR (95% CI) p-value
    Age (yr)
     <40 Ref.
     40–59 1.8 (0.976–3.157) 0.060
     ≥60 2.0 (0.960–4.096) 0.064
    Male sex 0.9 (0.541–1.409) 0.578
    Lesion size (mm)
     ≤5 Ref. Ref.
     5–10 2.0 (1.262–3.291) 0.004 2.3 (1.245–4.203) 0.008
    Multiple lesions 4.2 (0.841–21.389) 0.080 8.3 (1.247–54.774) 0.029
    Echogenicity in EUS
     Hypoechoic Ref. Ref.
     Indeterminate 0.2 (0.031–1.778) 0.160 0.2 (0.027–1.656) 0.138
    Treatment method
     Conventional EMR Ref. Ref.
     EMR-Sa) 0.5 (0.253–0.820) 0.009
     EMR-Pb) 1.6 (0.502–5.022) 0.432
     ESD 0.8 (0.263–2.148) 0.594
    Scope position
     Forward view Ref. Ref.
     Retroflexion view 2.7 (1.347–5.305) 0.005 4.0 (1.668–9.615) 0.002
    Table 1. Baseline characteristics and procedure outcomes

    Values are presented as mean±standard deviation or number (%).

    EUS, endoscopic ultrasonography; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection.

    Including muscularis mucosa and submucosa;

    including cold snare polypectomy (n=1);

    endoscopic mucosal resection with the strip biopsy method;

    endoscopic mucosal resection after circumferential precutting;

    In two cases, margin positivity was also confirmed.

    Table 2. Comparison of baseline characteristics between the complete and incomplete resection groups after endoscopic resection for rectal NET

    Values are presented as number (%) or mean±standard deviation.

    NET, neuroendocrine tumor; EUS, endoscopic ultrasonography.

    Including muscularis mucosa and submucosa.

    Table 3. Comparison of procedure outcomes between the complete and incomplete resection groups after endoscopic resection for rectal NET

    Values are presented as number (%) or mean±standard deviation.

    NET, neuroendocrine tumor; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; EUS, endoscopic ultrasonography; HPF, high-power fields; NA, not applicable.

    Including cold snare polypectomy (complete resection, n=9; incomplete resection, n=1);

    endoscopic mucosal resection with strip biopsy method;

    endoscopic mucosal resection after circumferential precutting.

    Table 4. Logistic regression analysis for determining factors associated with incomplete resection after endoscopic resection

    OR, odds ratio; CI, confidence interval; ref., reference; EUS, endoscopic ultrasonography; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection.

    Endoscopic mucosal resection with strip biopsy method;

    endoscopic mucosal resection after circumferential precutting.

    Table 1.

    Table 2.

    Table 3.

    Table 4.

    Clin Endosc : Clinical Endoscopy Twitter Facebook
    © Korean Society of Gastrointestinal Endoscopy.
    Close layer
    TOP