Introduction

The majority of pancreatic ductal adenocarcinomas (PDAC) are incurable at presentation but population-based screening is not recommended. Surveillance of asymptomatic high-risk individuals (HRI) with a strong family history or inherited pathogenic genetic variant associated with PDAC can lead to early detection but the survival benefit is unproven

Aims & Methods

We compared the overall survival (OS) and stage distribution of surveillance-detected PDACs in with a control population of patients with PDAC in the United States.
Methods: HRI enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 1998-2021 included individuals who had at >= 1 first-degree relative with PDAC, and who were part of a kindred with at least 1 pair of affected first-degree relatives (familial pancreatic cancer), or were carriers of a gene associated with hereditary pancreatic cancer (ATM, BRCA1, BRCA2, PALB2, STK11 or CDKN2A pathogenic germline variant and/or familial atypical mole melanoma FAMMM, Lynch syndrome, or Peutz-Jeghers syndrome. Those HRIs underwent surveillance with endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) and who developed PDAC were compared to matched control patients with PDAC in the National Cancer Institute (NCI) Surveillance, Epidemiology and End Resuts (SEER) Research Plus database. We matched SEER controls to each eligible CAPS case by age at diagnosis, gender, tumor location, and year-of-diagnosis and compared tumor stage and overall survival. We also performed sensitivity analyses to account for lead time bias and to compare resectable PDAC outcomes.

Results

Characteristic	CAPS PDAC Cases N=26	Matched SEER PDAC Controls N=1504	p value
American Joint Committee on Cancer (AJCC) stage - number (%)			< 0.001
1	10 (38.5%)	155 (10.3%)
2	8 (30.8%)	377 (25.1%)
3	1 (3.8%)	163 (10.8%)
4	7 (26.9%)	809 (53.8%)

A total of 1731 HRIs (mean age 60.3 years, 65% women, 52% familial pancreatic cancer relatives) enrolled in the CAPS surveillance program between 1998 and June 2021. 26 PDACs were diagnosed (mean age 65.8 years) at median or 5.8 years (range 1.1-11.2 years) from baseline. Fewer CAPS PDACs were well-differentiated and more were moderately to poorly differentiated compared to controls (5.3% vs. 14.4%, p=0,03). The PDAC size in the CAPS cohort was smaller than in controls (2.5 vs. 3.6cm p<0.001). Resectable T1 tumors (27.3%) were also more common in CAPS cases than in controls (T1 4.4%) (p<0.001). There was significant down-staging in the CAPS participants (38.5% AJCC Stage I, 30.8% Stage II) vs. controls (Stage I: 10.3%, Stage II: 25.1%, p<0.001). At diagnosis, only 26.9% of all CAPS PDACs were distantly metastatic, compared to 53.8% of controls (p=0.01). All CAPS participants who developed PDAC lived longer than 1504 controls (median overall survival (OS): 61.7 months CAPS vs. 8 months controls, 5-year OS: 50% CAPS vs 9% controls, p<0.001). Hazard ratios for the likelihood of death in all controls with PDAC (4.2,95% CI 2.3-7.6, p<0.001) as well as only resectable PDACs (HR = 3.3 95% CI 1.6, 6.7, p=0.001) compared to CAPS patients were comparable after accounting for 3-, 6-, and 12-month lead time bias.

Conclusion

Surveillance of asymptomatic HRI with EUS/MRI leads to detection of lower stage, smaller PDACs, with associated decreased mortality and improved survival in this cohort of patients. The very high long term survival rates for surveillance-detected PDAC are unlikely to be due to lead time bias.

Introduction

Endoscopic submucosal dissection (ESD) offers effective, en bloc resection of large colorectal lesions (1), but can be technically challenging, especially for lesions with poor access. This video showcases successful use of the saline-immersion/irrigation technique (SITE), double-balloon endoscopy (DBE) and a novel type of advanced imaging for resection of such a lesion, in a patient with a long sigmoid colon which compromised stability.

Aims & Methods

A 64-year-old woman was referred for evaluation of a sessile (Paris 0-Is) 80mm adenomatous lesion of the transverse colon. Focal surface irregularity (JNET 2B) was also identified. Multidisciplinary team discussion favored en bloc excision using ESD, under conscious sedation. Stable access to the lesion was challenging due to irreducible looping of the sigmoid colon, hindering any attempt at ESD using a standard colonoscope. A DBE was utilized to enhance access and stability, equipped with a conical short, transparent hood to allow for ESD using the pocket-creation method (PCM) (2-4) . ESD was performed using SITE (4-5), which offers several advantages: enhanced optical clarity and magnification, buoyancy of the lesion, improved conductivity (facilitating of vessel pre-coagulation and bleed-management). SITE also enhances patient comfort due to reduced distension, particularly when combined with external drainage of excess saline (6). Here, the DBE overtube was used for drainage. Severe fibrosis and muscle retraction was also observed at the center of the lesion, impeding access to the submucosal plane, this was overcome through clip-band traction. Additionally, a novel type of imaging: Amber-red color Imaging (ACI) (Fujifilm Healthcare, Tokyo, Japan), designed to enhance visualization of the muscularis propria and any vessels was also used, which further improved visualization of the dissection planes.

Results

The lesion was successfully resected en bloc in 180 minutes (dissection speed of 16.68 mm2/min), without significant adverse events. Hemostasias was achieved with knife-tip coagulation and intra-procedural application of protein-matrix gel coupled with scope-tamponade. The patient was prescribed a 5-day course of antibiotics and discharged on the same day. Histopathology confirmed a tubulo-villous adenoma with low-grade dysplasia, completely excised (R0).

Conclusion

DBE allows optimal access to challenging colonic lesions, where stability is critical for successful ESD. This example highlights the importance of adopting a tailored approach for each case, through a combination of established techniques, such as SITE, the PCM, and clip-band traction, to enhance ESD safety, efficacy and efficiency. Utilization of the latest-generation equipment, with optimized maneuverability, ergonomic comfort, and enhanced imaging, further supports these outcomes. Collectively, these strategies serve to overcome technically difficult scenarios.

References

1. Libânio D, Pimentel-Nunes P, Bastiaansen B, Bisschops R, Bourke MJ, Deprez PH, u. a. Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy. 29. März 2023;55(4):361–89
2. Hayashi Y, Sunada K, Takahashi H, et al. Pocket-creation method of endoscopic submucosal dissection to achieve en bloc resection of giant colorectal subpedunculated neoplastic lesions. Endoscopy 2014;46:E421-2
3. Hayashi Y, Miura Y, Yamamoto H. Pocket-creation method for the safe, reliable, and efficient endoscopic submucosal dissection of colorectal lateral spreading tumors. Dig Endosc 2015;27:534-5
4. Yamamoto H, Hayashi Y, Despott EJ. The pocket-creation method for endoscopic submucosal dissection combined with saline-immersion: another potential option to overcome challenges in colorectal endoscopic submucosal dissection. Gastrointest Endosc [Internet]. 1. August 2019 [zitiert 6. August 2023];90(2):288–9
5. Despott EJ, Murino A. Saline-immersion therapeutic endoscopy (SITE): An evolution of underwater endoscopic lesion resection. Digestive and Liver Disease [Internet]. 1. Dezember 2017 [zitiert 25. August 2023];49(12):1376. ​
6. Takaaki Morikawa, Alberto Murino, Hiroaki Ishii, Yoshikazu Hayashi, Yuka Kagaya, Hisashi Fukuda, Edward John Despott, Hironori Yamamoto. The ‘Asclepius tube’: a slim drainage tube wrapped around the distal part of the endoscope, for cecal endoscopic submucosal dissection, VideoGIE, 2024, ISSN 2468-4481

Disclosure

The authors declare the following conflict of interest:
EMB: No disclosures
GK: No disclosures
AR: No disclosures
AM: Personal payments/honoraria/fees: Olympus Medical, Laborie, Boston Scientific, Fujifilm Healthcare Europe
EJD: Educational grants in support of conference organization, and honoraria, from Fujifilm Healthcare Europe, Pentax, and Olympus Medical, and honoraria from Ambu and Fujifilm Healthcare Europe