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.

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

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

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

The number of colorectal cancer (CRC) cases and deaths in Japan is on the increase and is higher than in Western countries. In Europe and US, the increase in CRC among young people is a problem, in contrast to the decreasing trend among middle-aged and older people. In Japan, there is concern about the increase in CRC, and to prevent colorectal tumors (CRTs) in young people aged 40 years or younger, it is necessary to urgently understand the current situation and to carry out efficient screening by clarifying risk factors, together with CRC screening using fecal immunochemical test (FIT).

Aims & Methods

In this study, we conducted a retrospective study of the clinicopathological characteristics and risk factors of 303 CRTs diagnosed by colonoscopy (CS) at our institution in patients aged 40 years or younger.
(1) In the CRT group, the pathological diagnosis and location were investigated. (2) The examination period was divided into early (2012-2017) and late (2018-2024), and the frequency of tumor detection was examined. (3) The association of various background factors (family history of CRC, body mass index (BMI), hypertension (HT), dyslipidemia, diabetes, alcohol drinking, smoking and exercise habits) as risk factors for tumors was statistically investigated. SPSS29 (IBM) was used for statistical analysis.

Results

(1) CRTs included 237 adenomas, 38 serrated adenomas and 28 colorectal carcinomas (24 intra-mucosal carcinomas, 3 invasive carcinomas and 1 neuroendocrine tumor). Solitary tumors were 63.7% and 71.3% (89.3% for CRC) were located in the left colon. (2) The frequency of tumor detection was markedly increased: 2.04% in early male (M)/ 20.2% in late M and 0.29% in early female (F)/ 16.4% in late F. (3) Risk factors: overall risk factors for CRTs [odds ratio (OR) 95% confidence interval (CI)] were 2.998 (1.244-7.176) for family history of CRC, 1.786 (1.007-3.168) for BMI>30, 3.875 (1.082-13.878) for BMI>35, 2.456 (1.337-4.511) for HT, 1.596 (1.153-2.210) for alcohol drinking, 2.111 (1.306-3.412) for >20g/day alcohol drinking, 1.635 (1.170-2.285) for smoking. In M, risk factors for CRTs were family history of CRC 2.933 (1.036-8.300), HT 2.240 (1.124-4.463), alcohol drinking 1.760 (1.182-2.619, >20 g/day alcohol drinking 2.409 (1.402-4.138)) and in F, smoking 2.724 (1.223-6.070). In Logistic Regression, which added age and sex to the factors that were significant in univariate analysis, the risk factors for CRTs were: family history of CRC 3.542 (1.376-9.119), HT 2.032 (1.096-4.147), alcohol drinking 1.524 (1.076-2.159), smoking 1.665 (1.148-2.415).

Conclusion

The frequency of CRTs in young people aged 40 years or younger is increasing in Japan. Family history of CRC, HT, alcohol drinking and smoking are risk factors, and along with FIT, efficient screening based on these background factors is needed.

Introduction

Treatment of rectal cancer requires an understanding of presenting stage and therapeutic modalities to provide appropriate and effective multimodality approaches that are oncological sound and respectful in terms of organ preservation and survivors’ quality of life. Imaging (endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI)) determines the locoregional staging and optimal treatment for rectal cancer patients. However, for pT1 rectal cancer usually arising into a locally resectable polyp, the yield and role of this diagnostic techniques are no well-established.

Aims & Methods

Aim: To describe the use of locoregional staging and analyze its yield in a pT1CRC state-wide population-based cohort of pT1 rectal cancers.
Patients and methods: Nation-wide population-based cohort, multicenter study (EpiT1Consortium), including 33 centers from 12 different Spanish states. All pT1 CRC cases diagnosed between 2007-2018 were included regardless of the treatment received. Exclusion criteria were: histology other than adenocarcinoma, cancer hereditary syndromes, inflammatory bowel disease, synchronous and metachronous colorectal cancer in the previous 5 years, metastatic neoplastic disease at the time of diagnosis. Information on the demographic of the patient, diagnosis, staging, treatment, complications and histology of pT1 as well as a minimum of 2 years follow-up were collected. Multivariate analysis was performed using binary logistic.

Results

From 3161 patients of the EpiT1 cohort, 681 pT1 rectal cancer with complete information on staging were included for the analysis. 424/681(62.3%) underwent staging: 234(55.2%) with MRI only, 131(30.9%) MRI and EUS, 59(13.9%) only EUS. The characteristics independently associated with the staging (MRI and/or EUS) were: location in lower/middle vs upper rectum (69.1% vs 30.9%; OR 2.8[1.7-4 .5]), suspicion of invasive carcinoma at baseline colonoscopy (64.8% vs 35.2%; OR 2.6[1.6-4.2]), high risk vs low risk histology (69.5% vs 30.5%; OR 2.4[1,3-4,2]), patient management by other specialist (surgeon, oncologist, MDT) vs gastroenterologist (82.7% vs 17.3%; OR 2.2[1.3-3.7]). T staging was correct with MRI in 54/191(28,3%) and with EUS in 69/117(59%) and considering staging by MRI or EUS, 67.1% of patients were over-staged for the T. For N staging considering MRI or EUS the sensitivity and specificity were 15.4% and 82.6%, respectively (Table 1).

Table 1. Diagnostic accuracy for N: in MRI+EUS, only MRI and only EUS

Conclusion

The limited yield of locoregional staging imaging techniques should be taken into account when choosing the therapeutic strategy of suspected/known T1 rectal cancers. For T staging, considering the high rate of over-staging with imaging modalities, a stepwise approach using histopathology from a local en-bloc resection as a first step seems reasonable. For N staging, a major effort has to be performed to increase the yield of staging modalities in clinical practice.

References

• Toes-Zoutendijk E et al. Gut. 2018 Sep;67(9):1745-1746​​

• Verseveld M et al. Eur J Surg Oncol. 2021 48 (2022):1153-1160​​

• Keys MT et al. Int J Epidemiol. 2021 Mar 3;50(1):143-155​

• ​Benson AB et al . J Natl Compr Canc Netw 2022​​

• Chan et al. Gastrointestinal Endoscopy 2019

Disclosure

No

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.