Introduction

Duodenal Neuroendocrine Neoplasms (dNENs) are rare neoplasms (2.7% of all NENs) (1), but their incidence is on the rise. Most of them are smaller, low-grade neoplasms with an indolent course. The role of endoscopic resection and active surveillance of dNENs needs to be reviewed (2). The term neuroendocrine tumor (NET) generally refers to well-differentiated disease, neuroendocrine carcinoma (NEC) refers to poorly differentiated disease, and NEN is an umbrella term inclusive of both.

Aims & Methods

This is a single-center observational retrospective study of duodenal Endoscopic Band Ligation (dEBL) done between June 2020 and February 2023 at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India. The primary aim was to study the therapeutic efficacy of dEBL for dNENs. All patients having histological or molecular radiology (Gallium 68 DOTATEC) confirmation of a neuroendocrine neoplasm either at our center or outside were included. The size, number, and location of lesions were recorded. On histopathology examination, the grade and Ki 67 index were noted (3). The presence of lymph node, hepatic, and skeletal metastasis was assessed at the time of diagnosis through cross-sectional imaging and Gallium 68 DOTATEC scans (4). All patients underwent follow-up endoscopies 3–12 months after dEBL, and those who were indicated underwent repeat imaging.

Results

During the study period, n = 138 (M: F: 107:31, age: 53.92±11.95 years) patients underwent dEBL. Most lesions (90%) were non-functional and were incidentally diagnosed on endoscopy. The most common site was the first part of the duodenum and duodenal bulb (n = 123, 89%), with the majority of patients having single lesions (n = 118, 85%). The size of lesions (endoscopic or radiologic) was <1cm in n=110 (80%) patients. Diagnostic endoscopic ultrasound was done in n=82 (59%) patients and showed lesions arising from the 2^nd layer of the duodenum. Biopsy showed Well differentiated NENs (with or without duodenitis) in n = 108 (78%) patients, with a Ki67 index less than 3% in 61/92 (67%) patients. A DOTATEC scan done in n = 77 (56%) patients showed uptake in n = 37/77 (48%) patients. The mean SUV max was 23.61. Follow-up endoscopies were done in n = 104 (76%) patients at 3–12 months post-procedure, which showed complete clearance of the lesion in n = 92 (95%) patients (therapeutic efficacy). Twelve patients had residual lesions on endoscopic evaluation and underwent repeat DOTATEC scans, of which four showed residual lesions for which a repeat dEBL was done. Eleven patients (8%) had post-procedure upper abdominal pain, which subsided with conservative management.

Conclusion

Endoscopic duodenal banding should be considered a safe and effective treatment modality for all well-differentiated, low-grade dNENs after excluding metastases. Further prospective studies should be done to establish this modality as the gold standard of treatment and include it in the algorithm for the management of dNENs.

References

1. Modlin IM, Lye KD, Kidd M. A 5‐decade analysis of 13,715 carcinoid tumors. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2003 Feb 15;97(4):934-59.
2. Delle Fave G, Sundin A, Taal B, Ferolla P, Ramage JK, Ferone D, Ito T, Weber W, Zheng-Pei Z, De Herder WW, Pascher A. ENETS consensus guidelines update for gastroduodenal neuroendocrine neoplasms. Neuroendocrinology. 2016;103(2):119-24.
3. Zhang JY, Kunz PL. Making sense of a complex disease: A practical approach to managing neuroendocrine tumors. JCO Oncology Practice. 2022 Apr;18(4):258-64.
4. Pavel M, Öberg K, Falconi M, Krenning EP, Sundin A, Perren A, Berruti A. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020 Jul 1;31(7):844-60.

Introduction

Neuroendocrine tumors (NETs) are heterogeneous neoplasms originating from neuroendocrine cells, predominantly located in the gastrointestinal tract and pancreas. While surgical resection remains the primary curative intervention, a significant number of patients are ineligible for surgery due to comorbidities or the anatomical positioning of the tumor. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a minimally invasive alternative; however, the extant evidence is predominantly derived from small-scale case studies.

Aims & Methods

This multicenter study aims to comprehensively evaluate the efficacy, safety, and technical considerations of EUS-RFA in the management of NETs. A retrospective analysis was conducted on 45 patients with histologically confirmed neuroendocrine tumors (NETs) from five countries: Costa Rica, Egypt, India, Palestine, and Romania. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) was performed using a standardized 19-gauge RFA needle equipped with a 1 cm active-tip electrode. The primary outcomes assessed were treatment success, categorized as complete, partial, or failure. Secondary outcomes included the evaluation of complications and their correlations with tumor characteristics (such as grade, location, and histology), technical parameters (including power settings and ablation duration), and clinical factors. Statistical analyses were conducted using SPSS, employing Chi-square and Kruskal-Wallis tests.

Results

The cohort consisted of 53.3% females, with a mean age of 47.87 years. The overall complete ablation rate was 75.6%, with higher success rates observed for higher-grade tumors (G2/G3: 100% vs. G1: 80.8%). Tumor location significantly influenced outcomes, with pancreatic tail/neck lesions achieving 100% complete ablation compared to 58.8% for head lesions. Power settings of 35W, 40W, and 60W yielded 100% success, whereas 50W and 30W demonstrated lower efficacy (72.2% and 62.5%, respectively). Ablation duration tended to be longer in successful cases (mean 16.36 seconds) compared to failures (4.50 seconds). Insulinomas exhibited an 89.7% complete ablation rate, surpassing non-functioning NETs (50%). Complications were minimal, underscoring the procedure's safety.

Conclusion

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) represents a safe and efficacious minimally invasive approach for the treatment of neuroendocrine tumors (NETs), particularly in patients who present a high surgical risk. The success of this technique is contingent upon the biological characteristics of the tumor, anatomical considerations, and the precision of the procedure. Future research should aim to standardize protocols, integrate advanced imaging techniques, and investigate combination therapies to further enhance this promising intervention.

References

1. Oronsky B, Ma PC, Morgensztern D, Carter CA. Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas. Neoplasia 2017; 19: 991–1002. [DOI: 10.1016/j.neo.2017.09.002]
2. Verma SK, Khare R, Singh D. Current perspectives on neuroendocrine tumors. hLife 2024; 2: 563–575. [DOI: 10.1016/j.hlife.2024.07.006]
3. Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours. The Lancet Oncology 2008; 9: 61–72. [DOI: 10.1016/S1470-2045(07)70410-2]

Introduction

Red dichromatic imaging (RDI) is a next-generation image enhancement technique which works by employing green, amber and red wavelengths. The blood vessels in the deeper tissues absorb the amber light because of strong affinity with hemoglobin. Even though red light can penetrate deep into the tissue, it is weakly absorbed by hemoglobin. RDI enhances the visibility of deep blood vessels and bleeding sources. Hence it leads to early identification of bleeding sources and quicker hemostasis. RDI enhances the contrast between diluted blood and highly concentrated blood, thereby clearly visualizing the bleeding source. Bleeding during POEM is not very uncommon(0.5-0.7%). Early recognition of bleeding points and quicker hemostasis help in decreasing complications. The utility of RDI in the peroral endoscopic myotomy is not studied so far to our knowledge.

Aims & Methods

To assess the reduction in total procedural time using Red dichromatic imaging (RDI) compared to white light imaging in achieving haemostasis during POEM. To identifying avascular mucosal site by identifying and avoiding deep blood vessels using RDI, use of RDI in comparison with white light imaging (WLI) in achieving haemostasis, ease of mucosal entry by using RDI when compared to WLI and psychological stress experienced by endoscopists during haemostasis treatment.
A single centre prospective, randomized study conducted at tertiary referral centre. Patient with achalasia cardia who are undergoing POEM procedure are randomized into two groups- Group 1- Patient undergoing POEM using novel GF 1500 UGI Scope (RDI) and Group 2- patient undergoing procedure using regular white light endoscope. In group 1, RDI mode 2 was used for mucosal injection and incision and RDI mode 1 was used for identifying and controlling bleeding during the procedure.

Results

Achalasia cardia patients(n=103) undergoing POEM procedure where enrolled in this study, with 52 subjects in RDI Group and 51 subjects in WLI group. The mean age in the RDI group was 49.01± 14.78 years and in WLI group was 46.68± 15.58 years (p=0.32). The Eckardt score improved significantly in the both groups and adverse events where similar in both the groups. The total hemostasis time was significantly better (p=0.02) in the RDI group (7.9±12.02 sec) compared to WLI group (18.92±25.89 sec). Therefore the total procedural time was significantly quicker (p=0.02) in the RDI group when compared to the WLI group. However there was no significant advantage (p=0.18) of RDI over WLI in preventing mucosal entry point bleed. The RDI group had significant advantage in parameters like ease of entry (p=0.0001) and stress encountered by the operator (p=0.028).

Conclusion

Bleeding during POEM procedure can be daunting for even an experienced endoscopist and RDI can be helpful in this regard. The total hemostasis time, total procedural time, ease of submucosal entry and stress of the operator is seen to be significantly better using novel RDI. Hence RDI helps in early identification of bleeding sources and quicker hemostasis during POEM.

References

1. Maehata T, Fujimoto A, Uraoka T, Kato M, Horii J, Sasaki M, Kiguchi Y, Akimoto T, Nakayama A, Ochiai Y, Goto O. Efficacy of a new image-enhancement technique for achieving hemostasis in endoscopic submucosal dissection. Gastrointestinal Endoscopy. 2020 Sep 1;92(3):667-74.
2. Hirai Y, Fujimoto A, Matsutani N, Murakami S, Nakajima Y, Miyanaga R, Nakazato Y, Watanabe K, Kikuchi M, Yahagi N. Evaluation of the visibility of bleeding points using red dichromatic imaging in endoscopic hemostasis for acute GI bleeding (with video). Gastrointestinal Endoscopy. 2022 Apr 1;95(4):692-700.
3. Anudeep KV, Ramchandani M, Inavolu P, Nabi Z, Reddy DN. Red dichromatic imaging in peroral endoscopic myotomy: a novel image-enhancing technique. VideoGIE. 2021 May 1;6(5):203-6.

Introduction

LECS was reported by Hiki in 2008 as one of the treatments for gastric GIST (1). In 2012, our hospital introduced LECS for the treatment of superficial non-ampullary duodenal adenoma (SNADA) and non-ampullary neuroendocrine tumor (NADNET) using the same method (2). From 2021, D-LECS was divided into D-LECS with FTR, which is a full-thickness resection, and D-LECS with ESD, which is intended for post-ESD reinforcement (3).

Aims & Methods

The aim of this study was to extract cases in which D-LECS with ESD was performed at our hospital and to report the important points that should be noted in treatment. FAP cases were excluded in 99 eligible cases from January 2001 to October 2022. In addition, there were many cases in the follow-up group at SNADA. Of the 50 cases treated, there were 23 in the endoscopic treatment group, 16 in the LECS treatment group, and 11 in the surgical treatment group. There were 16 D-LECS cases, of which 4 cases for which D-LECS with ESD was performed were extracted. Before the D-LECS insurance coverage, the treatment was approved by the hospital ethics committee and the treatment was introduced.

Results

There were three points of view which were endoscopic aspects, laparoscopic aspects, and aspects to note throughout the treatment. Four examples revealed some important points. Case 1: Preoperative discussion was insufficient and D-LECS with ESD was decided at the time of surgery. It took nearly 2 hours to resect the lesion with an endoscope and then the laparoscopic side was sutured. After the treatment, it was possible to pass the endoscope through the treated area, but a few days later, a stenosis was formed, and endoscopic dilation was needed to improve. Case 2: Preoperative discussion was also insufficient. This case had many blood vessels, and the ST hood was needed because it is difficult to perform ESD. When the endoscope was extended, perforation occurred. Once the perforation was made, it was difficult to move the patient, so the muscle layer was sutured with OTSC, and a PGA sheet. Case 3: The endoscopic strategy and device were improved, and the lesion could be dissected within 1 hour. ESD was performed with Dual Knife J 1.5. Pulling the lesion with an S-O clip without using an ST hood so as not to apply strong pressure to muscle layer. The RDI function was used during hemostasis to avoid the burn effect on the muscle layer. On the other hand, there was a problem that the treatment site was unclear when suturing with a laparoscope. Case 4: Endoscope operation might be difficult, so a PCF scope was used for ESD. Blood vessels were densely existed on the upper the lesion, and the resection margin became unclear due to hemostasis. Lembert suture was added after a full-thickness suture due to a small perforation. 10 days after the operation, the peristalsis decreased, and the contents did not pass even though the endoscope passed. Most of these caveats have visions for improvement. Technical aspects and device selection can be overcome by referring to published literature. In addition, we believe that stenosis and passage obstruction can be improved with additional treatment because restenosis has not been observed in endoscopic dilatation. It was important to find an effective treatment for hypoperistalsis.

Conclusion

At present, there are a number of caveats that must be overcome on both the endoscopic side and the laparoscopic side. Therefore, even though D-LECS has been covered by health insurance, it is necessary to consider some strategy before treatment.

References

(1) Hiki N, Yamamoto Y, Fukuda T et al: Laparoscopic and endoscopoic cooperative surgery for gastrointestinal stromal tumor. Surg Endosc 22:1729-1735, 2008
(2) Hiroyuki Aoyagi, Naoyuki Ibe, et. al. The indication and limitation of Laparoscopy and endoscopy cooperative surgery (LECS) in the treatment of duodenal non-ampullary lesions. Endoscopia Digestiva, 2015, Vol. 27,No 9, p1565-1572
(3) Souya Nunobe, Motonari Ri, Naoki Hiki et al: Safety and Feasibility of laparoscopic and endoscopic cooperative surgery for duodenal neoplasm: a retrospective multicenter study. Endoscopy 53: 1065-1068, 2021

Disclosure

There was no Conflict of Interest.

Introduction

We previously reported short-term outcomes at 3 months after cold forceps biopsy (CFB) using jumbo biopsy forceps (Boston Scientific or Olympus Medical Systems) for micro-pharyngeal neoplasms¹.

Aims & Methods

We extended the follow-up and present here outcomes at 12 months after the CFB (UMIN registry number: 000037980). One hundred twenty-five lesions in 101 patients endoscopically diagnosed with narrow-band imaging of dilated intrapapillary capillary loops with clear demarcation as micro-pharyngeal tumors of 3 mm or less and excised with CFB were prospectively registered. After excluding 28 lesions with benign pathology, 97 lesions (13 lesions of squamous cell carcinoma, 4 of high-grade dysplasia, and 80 of low-grade dysplasia) were endoscopically followed up 3 and 12 months after the first CFB. Additional CFB was performed if lesions with endoscopically determined local remnant/recurrence (ER, narrow-band imaging of dilated intrapapillary capillary loops with clear demarcation) were found. The primary outcome was ER rate. The secondary outcome was composite remnant/recurrence (CR) (ER with pathological recurrence, ER without pathological assessment, and non-ER scars but with pathological recurrence) rate.

Results

Endoscopy at 3 months after CFB was performed in 56 lesions in 47 patients, and CFB scars were identified in 25 lesions (44.6%). Additional CFB was performed in all scars judged as ER, and regular biopsy was obtained in some scars without ER. ER rate at 3 months was 23.2% (13/56, 95% confidence interval 13 - 36.4%), and CR rate was also 23.2% (13/56, 13 -36.4%) (one ER scar with negative pathology, and one non-ER scar with positive pathology). Endoscopy at 12 months was performed in 84 lesions in 71 patients. CFB scars were identified in 20 lesions (23.8%); ER rate at 12 months was 11.9% (10/84, 5.9 -20.8%), and CR rate was 8.3% (7/84, 3.4-16.4%) (3 ER scars with negative pathology, no non-ER scar with positive pathology). Regarding safety of the procedure, no intraoperative or postoperative adverse event was observed in all the 125 lesions including 24 lesions excised under continued antithrombotic therapy.

Conclusion

About 10% remnant or recurrence rates at 12 months after the procedure suggest that CFB may be minimally invasive therapeutic option for micro-pharyngeal neoplasms of 3 mm or smaller. Further follow-up study is continuing.

References

1: Shimodate Y et al. Efficacy and safety of cold forceps biopsy for diminutive pharyngeal neoplasms: Single-center, prospective pilot study. Dig Endosc 2021; 33: 761-769.

Clinical Case Summary

Gastrointestinal neuroendocrine tumours (NETs) are low-grade malignant tumours in the GI tract. They account for 0.4% to 1.8% of GI malignancies. Duodenal NETs are relatively rare tumours and only accounts for 2% to 3% of GI NETs.
The patient, a 68 year old male, had dyspepsia and OGD showed a 10mm subepithelial lesion (SEL) (Insert image here) in the second part of the duodenum. Biopsies revealed polypoid foveolar hyperplasia. An endoscopic ultrasound (EUS) was done to evaluate the SEL which showed a 7mm x 8mm hypoechoic lesion within the submucosal layer (insert image). There was a slit within the SEL which corresponds to the previous biopsy sampling. Differentials were GIST or pancreatic rest. Further biopsies were taken from the within the slit which concluded as a well-differentiated NET, Grade 1.
PET DOTATE scan showed tracer-avid focus in the duodenum. Chromogranin A was elevated at 1056ug/L.
In view of previous sampling with a biopsy scar now, removal of the duodenal NET was carefully thought out. Endoscopic mucosal resection (EMR) has a higher risk of perforation due to the possibility of fibrosis from the biopsies. Laparoscopic endoscopic cooperative surgery was discussed with the surgeons, however, it is invasive.
Patient then underwent underwater EMR. The duodenal NET had sufficient buoyancy whilst underwater (Insert image). A 10mm snare was used, and polypectomy with Endocut Q mode done with good margins. There was no intraprocedural bleeding nor perforation. Two clips were used to close the polypectomy site prophylactically (Insert image).
Histology demonstrated tumour cells within the lamina propria and submucosa with salt and pepper like chromatin and round nuclei. They were positive for synaptophysin and chromogranin. Ki-67 index was 2%, and the margins were clear. This was conclusive of a NET Grade 1.
This case highlights the approach and differentials to duodenal lesions, and points to be considered for endoscopic resection in the duodenum.

References

Sato Y, Hashimoto S, Mizuno K, Takeuchi M, Terai S. Management of gastric and duodenal neuroendocrine tumors. World J Gastroenterol. 2016 Aug 14;22(30):6817-28
Gaspar JP, Stelow EB, Wang AY. Approach to the endoscopic resection of duodenal lesions. World J Gastroenterol. 2016 Jan 14;22(2):600-17
Wang X, Wu Y, Cao X, Zhang X, Cheng Y, Kong L. Duodenal neuroendocrine tumor: A rare case report. Medicine (Baltimore). 2021 Feb 12;100(6):e24635
Milione M, Parente P, Grillo F, Zamboni G, Mastracci L, Capella C, Fassan M, Vanoli A. Neuroendocrine neoplasms of the duodenum, ampullary region, jejunum and ileum. Pathologica. 2021 Feb;113(1):12-18