Introduction

Over the past two decades, there has been an increase in the incidence of rectal NET, which has in turn heightened the importance of optimizing its treatment and managing care after treatment. However, many cases of rectal NETs are removed by conventional EMR or even forceps polypectomy methods without being aware that it is NET which results in incomplete resection. Currently, no strong clinical evidence is supported for the need of salvage treatment in case of incompletely resected rectal NETs.

Aims & Methods

In this study, we aimed to find the factors that can predict the presence of remnant tumor after incomplete resection performed for the treatment of rectal NET in order to appropriately select patients who may require additional resection. We retrospectively reviewed clinical data of patients who underwent salvage treatment for incompletely resected rectal NETs between January 2010 and November 2023 at 5 tertiary hospitals.

Results

A total of 190 patients were enrolled in the study. Of these, 109 patients (57.4%) had a positive resection margin, while 81 patients (42.6%) had an indeterminate resection margin. 128 (67.4%) patients had no remnant tumor and 62 (32.6%) patients had remnant tumor at salvage resection specimen. The presence of remnant tumor varied according to the initial resection method used: 38.1% (16/42) for cold forcep polypectomy, 70.6% (24/34) for cold snare polypectomy, and 29.9% (26/87) for conventional EMR. Notably, no remnant tumors were found in patients who underwent modified EMR (n=21) or ESD (n=6) methods. Also, initial endoscopic resection performed by tertiary hospital expert showed significantly lower rate of remnant tumor compared to those performed by non-tertiary hospital expert with rate of 8.9% (4/45) and 40.9% (58/145) respectively. Lastly, patients with endoscopically remnant tumor before salvage treatment showed significantly higher rate of remnant tumor compared to those with endoscopically no remnant tumor with rate of 63.5%(47/74) and 12.9% (15/116) respectively. In multivariate analysis, endoscopic resection performed by non-tertiary expert (OR, 3.887; p=0.045) and endoscopically remnant tumor (OR, 10.891; p<0.001) were significant risk factors for the presence of remnant tumor.

Conclusion

Follow-up rather than resection may be considered for patients with positive resection margin after modified EMR or ESD for rectal NET. Also, endoscopic resection done by non-tertiary hospital expert and endoscopically remnant tumor are significant risk factors for the need of salvage treatment.

Introduction

Although the prognosis of low-grade rectal neuroendocrine tumors (NET) is good, surveillance of patients with pathologically incomplete resection after endoscopic resection (ER) remains controversial.

Aims & Methods

This study aimed to evaluate the long-term outcomes of patients with grade 1 rectal NET after ER and the risk factors for incomplete resection. We retrospectively enrolled patients who were diagnosed with rectal NET grade 1 after endoscopic resection between January 2011 and December 2023. We divided the patients into two groups according to histopathological evaluation: complete resection and incomplete resection. Patients who were followed up for > 12 months were included in the analysis. Logistic regression analysis was performed to investigate the risk factors for incomplete resection after ER.

Results

In total, 454 patients were enrolled in this study. Mean (SD) lesion size was 5.7 (2.1) mm and lesion location (distance from anal verge) was 7.8 (3.1) cm from anal verge. The most common treatment method was endoscopic mucosal resection with strip biopsy method (EMR–S, n = 338, 74.4%). On histopathologic evaluation after ER, the complete resection rate was 80.6% (n = 366). Of the incomplete resections (n = 88, 19.4%), 82 (18.1 %) were margin positive and 11 (2.4%) were lymphovascular invasion. Mean follow up months were 38.8 (27.3) and 46.2 (30.2) months in entire patients and incomplete resection group, respectively. In logistic regress analysis showed the lesion size 5.1 – 10 mm (OR 1.9, 95% CI 1.021– 3.686, P. = 0.044), multiple lesions (OR 8.9, 95% CI (1.454 – 71.165; P = 0.021), and retroflexion scope view (OR 4.3, 95% CI, 1.639 – 10.924; P = 0.002) were the independent risk factors associated with incomplete resection. During the follow-up period, despite the inclusion of patients with incomplete resection, no recurrence was observed.

Conclusion

Grade 1 rectal NET have a very good prognosis even with incomplete ER. Even if the resection is incomplete, progress can be observed without additional treatment.

Clinical Case Summary

Introduction: Rectal neuroendocrine tumors (NETs) are rare, asymptomatic or can have unique clinical manifestations. They represent 12% to 27% of all NETs, 20% of gastrointestinal NETs and 1.8% of all rectal neoplasms. They are slowly growing potentially malignant tumours, metastasizing in 10% to 15% of cases. Most rectal NETs are diagnosed incidentally during screening colonoscopy. Approximately 80% of them are 10 mm or less in size. For small (< 10 mm), endoscopic resection is recommended if there is no evidence of invasion beyond the submucosa or presence for regional disease. Lymph node metastasis is very rare, appearing in only 2.5% of tumors less than 10 mm.
Case report: 61-year-old male patient without any comorbidities concerns of skin flushing and abdominal pain for five years. Colonoscopy was performed in which was found yellowish, small, round, submucosal lesion, 5 mm in size with intact overlying mucosa in rectum on 10 cm above the anal verge. Hot snare polypectomy was made. Histopathology and immunohistochemistry findings: Rectal Neuroendoctine tumor, Low Grade (G1): 2 mitotes/10 HPFs and <2% Ki67 index, positive for S100, Vimentine, Sinaptophysin and negative for NSE, CK-20, CK-7. In whole-abdomen and thoracic computerized tomography, no distant metastasis was detected. Octreotide scan, blood test and Chromogranine A were with normal findings. After 12 months the patient was without symptoms, colonoscopy was performed with biopsy specimens from the resection margin, there was no residual tumor.
Conclusion: Rectal NETs smaller than 10 mm in size are usually low grade and can be successfully treated endoscopically.
Figure 1. Colonoscopy appearance of the rectal NET.
Figure 2. Histopathology of the rectal NET.

References

1. Ramage, J.K.; De Herder, W.W.; Delle Fave, G. Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms. Neuroendocrinology 2016; 103:139–143.
2. Maione F, Chini A, Milone M, Gennarelli N, Manigrasso M, Maione R, Cassese G, Pagano G, Tropeano FP, Luglio G, De Palma GD. Diagnosis and Management of Rectal Neuroendocrine Tumors (NETs). Diagnostics. 2021; 11(5):771.
3. Gallo C, Rossi RE, Cavalcoli F, Barbaro F, Boškoski I, Invernizzi P, Massironi S. Rectal neuroendocrine tumors: Current advances in management, treatment, and surveillance. World J Gastroenterol 2022; 28(11): 1123-1138
4. Yangong H, Shi C, Shahbaz M, Zhengchuan N, Wang J, Liang B, Ruliang F, Gao H, Bo Q, Niu J. Diagnosis and treatment experience of rectal carcinoid (a report of 312 cases). Int J Surg. 2014;12(5):408-11
5. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20;26(18):3063-72.
6. Viana C, Marques I, Staubus A, Martins S. Rectal carcinoid tumor: diagnosis and management. Journal of Coloproctology 2019; 39(02):184-89.

Disclosure

Authors have no conflicts of interest to declare.

Introduction

Risk factors for rectal neuroendocrine tumor (NET) has not been reported in a cohort setting, even if their association was reported in a cross sectional study. We investigated sex-specific risk factors of rectal NET in a population-based cohort.

Aims & Methods

This is a population-based cohort study. Cancer and NET-free individuals who underwent general health examination during 2010 at the Korean National Health Insurance Service were enrolled and followed through 2017. Many epidemiologic factors and lipid were evaluated. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) determined by Cox regression analysis were used to investigate risk of NET.

Results

Rectal NET was newly detected in 2339 of 5.522 million individuals. In adjusted analysis, male sex (HR, 1.32; 95% CI, 1.17-1.48), current smoker (HR, 1.19), past smoker (HR,1.14), and obesity (HR, 1.462; 95% CI, 1.01-2.11 in BMI >=30) increased the risk of rectal NET. Frequent alcohol consumption increased the risk of rectal NET with dose dependent manner (HR, 1.36 in 1/week, 1.47 in 2-3/week, 1.54 in 4-5/week, 1.16 in >=6/week). In men, current smoker, past smoker, frequent alcohol consumption, and obesity (HR, 2.51; 95% CI, 1.41-4.45 in BMI >=30) increased the risk of NET. In women, past smoker (HR, 1.65), frequent drinker, and previous hysterectomy history (HR, 1.54; 95% CI, 1.16-2.03) increased the risk of rectal NET. Younger age was associated with rectal NET risk in both men and women.

Conclusion

Younger age, smoking, frequent alcohol consumption increased the risk of rectal NET in both men and women, whereas obesity markedly increased rectal NET in men but not in women. In women, previous hysterectomy history increased the risk of rectal NET.

Introduction

A positive resection margin after endoscopic submucosal dissection (ESD) of a colorectal neoplasm is associated with an increased risk of recurrence. However, it may be caused by cauterization or tangential specimen cutting. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD.

Aims & Methods

We reviewed 1010 patients who underwent colorectal ESD at two hospitals between 2015 and 2020. The inclusion criteria were that the patient 1) had an en bloc resection, 2) had at least one follow-up colonoscopy. The recurrence rates and presence of residual tumors in the surgical specimens were evaluated.

Results

A total of 632 patients were enrolled. Among them, 557 patients had complete resections, and 75 had incomplete resections with positive resection margins in vertical and/or horizontal margin. The rate of additional surgery after ESD and recurrence was significantly higher in patients with incomplete resection compared to patients with complete resection. However, in patients with non-invasive colorectal neoplasm, all 411 patients, including those with complete and incomplete resection, had no recurrence. Among 221 patients with invasive lesions, 39 underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with remnant tumors in the surgical specimen. Lymphovascular invasion was associated with lymph node metastasis. However, no remnant tumor nor lymph node metastases were found in patients with only one unfavorable histological factor, including 1) positive vertical margin, 2) a submucosal invasion depth > 1000 µm, 3) lymphovascular invasion, 4) poorly differentiated cancer, and 5) high tumor-budding grade.

Conclusion

A positive resection margin after en bloc colorectal ESD for noninvasive lesions was not associated with recurrence. In T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Introduction

The incidence of rectal neuroendocrine tumors (rNETs) has risen over the past two decades, largely due to the increased use of endoscopic procedures. These tumors are typically small, well-differentiated, and associated with a favorable prognosis. However, up to 82% may be misdiagnosed, leading to inadequate treatment. Accurate staging and appropriate management are essential for achieving long-term, progression-free survival (PFS) [1-2].

Aims & Methods

This study evaluates the clinical outcomes of patients with rNETs ≤1 cm who underwent local excision.
This retrospective, dual-center study included patients with rNETs measuring ≤10 mm who underwent local excision. The primary endpoint was PFS. Resection techniques were categorized into two groups based on guideline recommendations: recommended (m-EMR, ESD, EFTR, and TAMIS/TEMS) or not recommended (biopsy forceps and hot/cold snare polypectomy). Statistical analyses were performed using MedCalc software, with significance set at p < 0.05.

Results

Among 101 patients initially evaluated, 91 were included after excluding 10 due to incomplete endoscopic follow-up. The cohort consisted of 51 men (56%) and 40 women (44%), with a median age of 53 years. The median tumor size was 5 mm (range: 1–10 mm). Tumor grading was G1 in 93.4% of cases and G2 in 6.6%, with a median Ki-67 index of 2%.
Recommended resection techniques were used in 34 patients (37.4%), while 57 patients (62.6%) underwent non-recommended methods. Positive R1 resection margins were found in 27 cases (29.7%), and lymphovascular invasion was detected in two cases. Tumor progression (defined as recurrence, increase in residual tumor following R1 resection, or development of metastasis) occurred in 15 patients (16.5%), with only one case progressing to lymph node metastasis (median time to progression: 14 months [1–108 months]). Two deaths were recorded, neither related to the tumor. The median progression-free survival was 28 months (range: 1–170 months).
Univariate analysis showed that the use of recommended resection techniques significantly improved prognosis (HR 0.12, p = 0.04).

Conclusion

Although rNETs measuring ≤10 mm can recur, their risk of metastatic progression remains low, confirming their indolent behavior. However, early detection and the choice of appropriate resection techniques are essential for optimizing patient outcomes. Guideline-recommended resection methods are linked to a lower risk of progression and should be the preferred approach in clinical practice.

References

1. Rinke A, Ambrosini V, Dromain C, Garcia-Carbonero R, Haji A, Koumarianou A, van Dijkum EN, O'Toole D, Rindi G, Scoazec JY, Ramage J. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours. J Neuroendocrinol. 2023 Jun;35(6):e13309.
2. Fine C, Roquin G, Terrebonne E, Lecomte T, Coriat R, Do Cao C, de Mestier L, Coffin E, Cadiot G, Nicolli P, Lepiliez V, Hautefeuille V, Ramos J, Girot P, Dominguez S, Céphise FV, Forestier J, Hervieu V, Pioche M, Walter T. Endoscopic management of 345 small rectal neuroendocrine tumours: A national study from the French group of endocrine tumours (GTE). United European Gastroenterol J. 2019 Oct;7(8):1102- 1112.

Introduction

Neuroendocrine neoplasms are a group of tumors originating from neuroendocrine cells and peptidergic neurons. Rectal neuroendocrine tumors (NETs) are the second most common location for gastrointestinal NETs, albeit representing only 2% of all rectal neoplasms. Most of these are nonfunctional and asymptomatic although pain, blood loss and perianal discomfort can occur in larger lesions.
Endoscopically, rectal NETs typically appear as small and well-delimited submucosal lesions, with a yellowish color. The risk of lymph node metastasis is related to the tumor size, therefore, the current guidelines consider endoscopic resection as an option for rectal NETs smaller than 2 centimeters. The classical options for lesion removal include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, EMR has a higher risk of incomplete resection, whereas ESD is more invasive and has an increased risk of complications (namely bleeding and perforation).
In this setting, underwater endoscopic mucosal resection (UEMR) appeared as an alternative that facilitates the complete removal of a lesion through the filling of the intestinal cavity with water. Previous Eastern studies suggest a higher complete resection rate with this endoscopic technique when compared to conventional EMR.

Aims & Methods

The present study aimed to evaluate the outcomes of patients submitted to UEMR of rectal NETs in a reference center.

Results

A total of 5 patients underwent UEMR for rectal NETs (Table 1). 3 patients had a tumor from the proximal rectum and 2 patients from the distal rectum. The tumor size ranged between 4 and 8 millimeters.
After marking the lesion borders, the entire rectal cavity was filled with saline and UEMR was performed. The lesion scar was closed with endoscopic clips in all cases. In a single case, delayed rectal bleeding was observed 3 days after procedure, solved with application of an additional endoscopic clip, without the need of inpatient management. No other complications were reported.
A R0 resection was observed in 80% of the cases. In a single case a positive basolateral margin was observed. However, after performance of a second UEMR in the scar (where no endoscopic evidence of residual lesion was found), there was absence of lesion in the histopathological sample. All the tumors had a G1 grade in the WHO 2019 Classification for Neuroendocrine Tumors, with a Ki-67 index ranging between 1 and 3%.
In all the cases there was absence of residual lesion or recurrence in the follow up endoscopy.

Conclusion

This case series showcases UEMR as an effective alternative to conventional EMR, achieving high satisfactory complete resection rates, while having a low rate of procedure related complications. Therefore, UEMR should be contemplated when considering an endoscopic removal for rectal neuroendocrine neoplasms.

References

1. Rinke, Anja et al. “European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours.” Journal of neuroendocrinology vol. 35,6 (2023)
2. Srirajaskanthan, Rajaventhan et al. “Optimising Outcomes and Surveillance Strategies of Rectal Neuroendocrine Neoplasms.” Cancers vol. 15,10 2766. 15 May. 2023
3. Shi, Haitao et al. “Underwater endoscopic mucosal resection for rectal neuroendocrine tumors (with videos): a single center retrospective study.” BMC gastroenterology vol. 22,1 276. 2 Jun. 2022
4. Okada, Masahiro et al. “Underwater Endoscopic Mucosal Resection of Small Rectal Neuroendocrine Tumors.” Frontiers in medicine vol. 9 835013. 19 Apr. 2022