Introduction

Endoscopic submucosal dissection is becoming the gold standard for the resection of superficial squamous cell carcinoma. It is unclear whether delaying esophgectomy after endoscopic submucosal dissection is better in terms of mortality and complications than primary esophgectomy in esophageal cancer patients. We compared the long-term outcomes and the complications between these two groups.

Aims & Methods

Between 2003 and 2019, 191 patients underwent primary esophagectomy and 65 patients underwent ESD then delayed esophagectomy. In a matched group of 65 pairs, OS, DSS, and RFS were compared between the 2 groups. The overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and postoperative complications were compared between the propensity-matched groups.

Results

In a matched cohort, OS, DSS, and RFS were comparable between the 2 groups. Even though the overall survival of 6 years was 70% versus 80% (p value=0.041) in the primary esophgectomy versus ESD and consequent esophgectomy respectively, DSS was 25% versus 12.5% (p value=0.21). The RFS was 80% versus 98% with p value of 0.06. In terms of recurrence free survival, differentiation, and tumor size were independent factors. When comparing adverse events between two groups there were non 60 day mortality in both groups and significant difference in early complication in the primary surgery group compared to surgery after ESD group. (47.7% versus 15.4%, p=<0.001)

Conclusion

In management for the superficial esophageal cancer, delayed surgery may have advantage in terms of survival, recurrence-free survival and complications.

References

1. Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Dicker D, et al. The global burden of cancer 2013. JAMA Oncol 2015;1:505-27.
2. Steffen T, Dietrich D, Schnider A, et al. Recurrence patterns and longterm results after induction chemotherapy, chemoradiotherapy, and curative surgery in patients with locally advanced esophageal cancer. Ann Surg. Epub 2017 Jul 24.
3. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366:2074-84
4. Ra J, Paulson EC, Kucharczuk J, et al. Postoperative mortality after esophagectomy for cancer: development of a preoperative risk prediction model. Ann Surg Oncol 2008;15:1577-84.
5. Chang AC, Ji H, Birkmeyer NJ, et al. Outcomes after transhiatal and transthoracic esophagectomy for cancer. Ann Thorac Surg 2008;85: 424-9.
6. Connors RC, Reuben BC, Neumayer LA, et al. Comparing outcomes after transthoracic and transhiatal esophagectomy: a 5-year prospective cohort of 17,395 patients. J Am Coll Surg 2007;205:735-40.
7. Takahashi H, Arimura Y, Masao H, et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc 2010;72:255-64

Introduction

Capsule endoscopy (CE) is a minimally invasive exam suitable of panendoscopic evaluation of the gastrointestinal tract. Nevertheless, CE is time-consuming, with suboptimal diagnostic yield in the upper GI tract. Convolutional neural networks (CNN) are human brain architecture-based models suitable for image analysis. However, there is no study about their role in capsule panendoscopy.

Aims & Methods

Our aim was to develop an artificial intelligence (AI) model for panendoscopic automatic detection of pleomorphic lesions (namely vascular lesions, protuberant lesions, hematic residues, ulcers, and erosions). 355110 images (6977 esophageal, 12918 gastric, 258443 small bowel, 76772 colonic) from eight different CE and colon CE (CCE) devices were divided into a training and validation dataset in a patient split design. The model classification was compared to three CE experts’ classifications. The model’s performance was evaluated by its sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the precision-recall curve.

Results

The binary esophagus CNN had a diagnostic accuracy for pleomorphic lesions of 83.6%. The binary gastric CNN identified pleomorphic lesions with a 96.6% accuracy. The undenary small bowel CNN distinguished pleomorphic lesions with different hemorrhagic potential with 97.6% accuracy. The trinary colonic CNN (detection and differentiation of normal mucosa, pleomorphic lesions, and hematic residues) had 94.9% global accuracy.

Conclusion

Our group developed the first AI model for panendoscopic automatic detection of pleomorphic lesions in both CE and colon CE from multiple brands, solving a critical interoperability technological challenge. Deep learning-based tools may change the landscape of minimally invasive capsule panendoscopy.

References

1. Pennazio M, Rondonotti E, Despott EJ, Dray X, Keuchel M, Moreels T, et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2023 Jan;55(1):58-95. PubMed PMID: 36423618. Epub 20221124.
2. Le Berre C, Trang-Poisson C, Bourreille A. Small bowel capsule endoscopy and treat-to-target in Crohn's disease: A systematic review. World J Gastroenterol. 2019 Aug 21;25(31):4534-54. PubMed PMID: 31496630. PMCID: PMC6710184.
3. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature. 2000 May 25;405(6785):417. PubMed PMID: 10839527.
4. Rondonotti E, Pennazio M. Colon capsule for panendoscopy: a narrow window of opportunity. Endosc Int Open. 2021 Dec;9(12):E1860-E2. PubMed PMID: 34917450. PMCID: PMC8670997. Epub 20211214.
5. Vuik FER, Moen S, Spaander MCW. Colon capsule endoscopy as panendoscopy: Using current knowledge to enhance possibilities. Endosc Int Open. 2022 May;10(5):E584. PubMed PMID: 35571484. PMCID: PMC9106432. Epub 20220513.

Introduction

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been widely used as a safe and effective method for obtaining samples from Solid masses around the gastrointestinal tract. It is difficult for endosonographers to determine the timing of termination of EUS-FNA. However, several reports have validated macroscopic on-site evaluation (MOSE) as safe and effective.

Aims & Methods

We performed a prospective pilot study to explore the value of MOSE in evaluating the specimen quality during magnifier-based EUS-FNA and confirm the cut-off length of visible tissue core (VTC). 79 consecutive patients who underwent EUS-FNA of solid masses around the gastrointestinal tract using 22-G needles were included in the study. After EUS-FNA, endosonographers used a special observation table to on-site evaluate all puncture specimens. Then, the specimens containing VTC were prepared into cell block and stained with haematoxylin-eosin (HE). Pathologists explored the relationship between VTC length and specimen quality. Finally, the receiver-operating characteristic (ROC) curve of the VTC length, with respect to the final diagnoses were plotted, and the accuracy of the area under the curve (AUC) for diagnostic yield was evaluated and to determine the optimal cut-off VTC length with the Youden index. The utility of optimal cut-off VTC length in diagnosis was investigated.

Results

1. In this study, EUS-FNA was performed on 93 masses in 79 patients, with a total number of needle passes of 249, including 221 needle passes (88.8%) containing VTC. The completion rate of EUS-FNA was 100% and the complication rate was 1.1%. Assisted by MOSE, the sensitivity, specificity, positive predictive value, negative predictive value and histological diagnostic rate of EUS-FNA in this study were 85.9% (73/85), 100.0% (8/8), 100.0% (73/73), 40.0% (8/20) and 87.1% (81/93), respectively. The kappa statistic indicated quite high agreement between EUS-FNA histologic diagnoses and final diagnoses (Kappa=0.511, P<0.05).
2. The pathologist scored the specimen and correlation analysis was performed by Spearman’s rank-order correlation. It is concluded that a positive correlation between specimen quality (integrity of tissue structure) and VTC length (rs=0.427, P<0.05). The ROC curve of the VTC length showed the cut-off VTC length of 7.45 mm with area under the curve of 0.838. With this cut-off level, the sensitivity and specificity of EUS-FNA were 80.8% and 66.7%, respectively.
3. Multivariate analyses of factors affecting the tissue diagnostic rate of EUS-FNA were performed. Inclusion factors were the maximum diameter of lesion, location of lesion, puncture method and the VTC length. The statistical results indicated that the VTC length ≥7.45mm and the maximum diameter of lesion were associated with the higher diagnostic rate of histopathology. However, the tissue diagnostic rate was not related to the location of lesion and puncture method.

Conclusion

1. MOSE could help endosonographers better assess specimen quality, so as to predict the specimen adequacy independently. We determined that the histological diagnostic yields were significantly improved when the VTC lengths obtained by EUS-FNA ≥7.45mm.
2. MOSE based on magnifying glass is practical for improving the specimen quality and reducing the number of needle passes when ROSE is unavailable. It is a safe, effective and economical diagnostic method for the solid masses around the gastrointestinal tract.

References

1. Iglesias-Garcia J, Dominguez-Munoz JE, Abdulkader I, et al. Influence of on-site cytopathology evaluation on the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic masses. Am J Gastroenterol 2011;106:1705-10.
2. Iglesias-Garcia J, Larino-Noia J, Abdulkader I, et al. Rapid on-site evaluation of endoscopic-ultrasound-guided fine-needle aspiration diagnosis of pancreatic masses. World J Gastroenterol 2014;20:9451-7.
3. Leung Ki EL, Lemaistre AI, Fumex F, et al. Macroscopic onsite evaluation using endoscopic ultrasound fine needle biopsy as an alternative to rapid onsite evaluation. Endosc Int Open 2019;7:E189-E194.
4. Iwashita T, Yasuda I, Mukai T, et al. Macroscopic on-site quality evaluation of biopsy specimens to improve the diagnostic accuracy during EUS-guided FNA using a 19-gauge needle for solid lesions: a single-center prospective pilot study (MOSE study). Gastrointest Endosc 2015;81:177-85.
5. Ishiwatari H, Sato J, Fujie S, et al. Gross visual inspection by endosonographers during endoscopic ultrasound-guided fine needle aspiration. Pancreatology 2019;19:191-195.

Disclosure

The authors have nothing to disclose.

Introduction

Esophageal squamous cell carcinoma (ESCC) can be treated curatively with definitive chemoradiotherapy (CRT). However, local failure, characterized by residue just after CRT or recurrence after achieving complete response with CRT, occurs in 20-40% of patients who received this treatment. Salvage endoscopic therapy is one of the treatment options for cT1N0N0 local failure after CRT or radiotherapy (RT) for ESCC, but most reports on its outcomes are at single center.

Aims & Methods

This multicenter study aimed to clarify the short- and long-term outcomes of salvage endoscopic therapy (endoscopic resection [ER: EMR/ESD] and photodynamic therapy using Talaporfin Sodium [PDT]) for cT1N0M0 local failure after CRT/RT for ESCC, and to identify factors that influence the outcomes of salvage endoscopic therapy. Patients who underwent salvage endoscopic therapy (ER, PDT) for cT1N0M0 local failure after CRT/RT for ESCC at two institutions between December 2012 and August 2021 were retrospectively investigated. The patients were excluded if they were not followed up for more than three months after salvage therapy or had a history of salvage therapy. The selection of the procedure was primarily based on the depth of the tumor and the degree of submucosal fibrosis.

Results

A total of 168 patients were analyzed, of which 86 underwent ER (EMR/ESD = 15/71) and 82 underwent PDT. Among the patients, 140 were male, and the median age was 72 (range: 45-88) years. Lesion characteristics were as follows: The clinical T stage before CRT/RT; T1a/T1b/T2/T3/T4a/unknown = 5/78/24/48/9/4 cases. Local failure before salvage therapy; residual/local recurrent lesions = 107/61 cases. Clinical tumor depth before salvage therapy; EP-LPM/MM-SM1/SM2-SM3 = 54/35/79 cases. 53 of the 54 patients with a tumor depth of EP-LPM underwent ER, while 73 of the 79 patients with a tumor depth of SM2-SM3 underwent PDT. The local complete response rate in PDT was 62% (50/81 patients, 1 not evaluated), and the R0 resection rate in ER was 73% (63/84 patients, 2 not evaluated due to burn effect). One patient in the PDT group died from massive gastrointestinal bleeding due to esophageal-aortic fistula on the 69th day after PDT. The median observation period was 33.5 (2-109) months, and the three-year overall survival (OS), disease-specific survival, local recurrence-free survival (LRFS), and esophagectomy-free survival rates were 79% (95% confidence interval: 71-86%), 88% (80-93%), 54% (46-62%), and 76% (67-82%), respectively. Multivariate analysis revealed that age ≥75 years and residual lesion just after CRT were independent risk factors of OS (p = 0.039 and p = 0.024, respectively). Clinical tumor depth was not a significant risk factor for OS and LRFS. The clinical course after salvage treatment was as follows: 93 patients had no recurrence; 28 patients had lymph node and/or distant metastatic recurrence with/without local failure. Of the 53 patients with local failure (residual: 33, local recurrence: 20) after initial salvage endoscopic therapy, 46 underwent re-salvage therapy (ER: 11, PDT: 27, surgery: 8), and 24 of them are alive without the recurrence of ESCC, while 8 died from the primary disease.

Conclusion

Our results suggest that salvage endoscopic therapy including ER or PDT appears to be an effective treatment option for cT1N0M0 local failure after CRT/RT, regardless of clinical tumor depth, resulting in a certain number of patients achieving long-term survival without the primary disease and preserving their esophagus.

Introduction

The duodenum plays a key role in regulating metabolism and is known to be dysfunctional early in the development of metabolic diseases such as type 2 diabetes (T2D). Duodenal mucosal resurfacing (DMR) is a non-pharmacologic, investigational, endoscopic treatment designed to hydrothermally ablate the duodenal mucosa to restore the metabolic functionality of the duodenum in people with T2D. DMR has a CE mark, reimbursement in select medical centres in Germany, and has been evaluated in over 300 patients to date with favorable safety and metabolic benefits observed. As part of the currently enrolling, global, pivotal Revitalize 1 trial for DMR, competency-based training and implementation have evolved to support scalable education of advanced-endoscopist investigators.

Aims & Methods

Here, we describe the current endoscopist training program for DMR, demonstrate its alignment with the European Society of Gastrointestinal Endoscopy¹ and the American Society for Gastrointestinal Endoscopy² training and effectiveness principles, and provide evidence that training methodology for DMR has led to acceptable and consistent safety outcomes in Revitalize 1. The training program consists of three core elements designed to enhance advanced-endoscopist proficiency toward safe and efficacious execution of the DMR procedure:
1) Structured didactic overview of the DMR system, procedure, and core competencies;
2) Initial hands-on tracking of the DMR catheter through the validated DMR training simulator; and
3) Hands-on live-patient cases focused on the successful execution of the DMR procedure and demonstration of core competencies.
The DMR simulator was developed and validated to complement the didactic component of the training program and recapitulate endoscopy skills necessary to perform the procedure as intended. Successful training was defined as completion of the full program with demonstration of competency in core DMR skills and troubleshooting techniques using the simulator. Procedural success was defined as performing ablations along the anatomical length of the duodenum from immediately beyond the ampulla of Vater to the Ligament of Treitz, while minimizing longitudinal gaps between areas of ablated mucosa.

Results

The DMR training program has been used to train therapeutic endoscopists in 6 centres in the EU and US as investigators in Revitalize 1. All centres successfully completed training in ~3 hours within 2 weeks of the first case. Nine open-label patients have been treated, to date, with 100% procedural success rate. Baseline characteristics were consistent with uncontrolled T2D despite multiple glucose‑lowering medications and insulin: 66.7% male, median (min, max), age 60 (45, 68) years, HbA1c 8.5% (7.6%, 9.1%), weight 96 (85, 128) kg, and diabetes duration 13 (7, 24) years. Adverse events (AEs) definitely or probably related to the device and/or procedure included sore throat (n=2), abdominal bloating (n=1), and abdominal pain (n=1). AEs were mild and resolved without sequalae. No observed long-term device- or procedure-related AEs, no device- or procedure-related SAEs, and no unanticipated AEs have been observed to date.

Conclusion

The three core elements of the DMR training program, inclusive of the DMR simulator, are scalable and have been reproducibly employed to train advanced therapeutic endoscopists to safely perform the DMR procedure. Results thus far suggest that DMR appears to be a safe, broadly accessible, and disease‑modifying approach to treat metabolic disease, such as T2D, via therapeutic endoscopy.

References

¹Boškoski et al. Curriculum for bariatric endoscopy and endoscopic treatment of the complications of bariatric surgery: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2023 Mar;55(3):276-293.
²Yang et al. The status of training in new technologies in advanced endoscopy: from defining competence to credentialing and privileging. Gastrointest Endosc. 2020 Nov;92(5):1016-1025.

Disclosure

IB: consultant–Apollo Endosurgery, Boston Scientific, Cook Medical, ERBE Elektromedizin; lecturer–Boston Scientific, Cook Medical, Microtech; grants–Apollo Endosurgery, Erbe Elektromedizin. CG: speaker–Intuitive Surgical (Proctor), BD, WL Gore, Medtronic. JV: consultant–Boston Scientific, Aspero Medical; research funding–Olympus America. MAG: research support/contracted research–Olympus America, Fractyl, Allurion Technologies; Consultant–Boston Scientific, Ambu. ES, KW, and HR: employees and shareholders of Fractyl Health, Inc. RS: Boston Scientific, Cook Medical, Intuitive Surgical.

Introduction

The early diagnosis of pancreatic cancer has long been considered a major clinical challenge. Recently in Japan, imaging-based screening strategies focusing on indirect findings have ushered in a new era, enabling the detection of carcinoma in situ and high-grade pancreatic intraepithelial neoplasia (PanIN). This study aimed to elucidate the molecular evolutionary mechanisms of PanIN development and progression.

Aims & Methods

We conducted detailed histopathological analysis and multi-regional genomic sequencing on 33 lesions obtained from a single patient with a family history of pancreatic cancer. The patient initially underwent distal pancreatectomy for a branch duct-type intraductal papillary mucinous neoplasm (IPMN) accompanied by adjacent main pancreatic duct (MPD) stenosis, followed by remnant pancreatectomy four years later due to newly detected ductal irregularities. The analyzed lesions included 15 low-grade PanINs, 14 high-grade PanINs, two low-grade IPMNs, and two concomitant pancreatic ductal adenocarcinoma components. Molecular analyses included KRAS and GNAS mutation detection using droplet digital PCR, targeted sequencing using a pancreatic cancer-related gene panel, and whole-exome sequencing. Tumor phenotypes were assessed by immunohistochemistry.

Results

Among numerous low-grade PanINs harboring various KRAS mutations, four distinct multicentric high-grade PanINs arose in the pancreatic body and tail. These included a laterally spreading high-grade PanIN within the stenotic MPD, characterized by KRAS G12D, TP53 deletion, and GATA6 Y83TfsX54; and three discrete high-grade PanINs located in branch ducts, all harboring KRAS G12V accompanied respectively by TP53 Y107D; TP53 S241F and ARID1A Q386X and S2096X; and TP53 G245S and ARID1A Q1066X. A low-grade gastric-type IPMN harboring KRAS G12R was determined to be clonally independent from the adjacent high-grade PanINs. A low-grade PanIN with KRAS G12D was identified at the pancreatic cut margin, though it showed no evidence of malignancy. In the remnant pancreatic head, a high-grade PanIN harboring KRAS G12D, TP53 deletion, and GATA6 Y83TfsX54—identical to the dominant clone in the pancreatic body—had extended along the MPD from the ductal stump to the ampulla. Two small invasive carcinoma foci were found to be continuous with this high-grade PanIN and shared identical KRAS, TP53, and GATA6 mutations, along with additional copy number variations affecting several genes. Another small high-grade PanIN with KRAS G12D and TP53 C275Y was identified in a neighboring branch duct. Furthermore, a germline CDKN2A H66R variant was detected, suggesting a potential hereditary predisposition to pancreatic tumorigenesis. The patient has remained recurrence-free for four years following the remnant pancreatectomy.

Conclusion

In high-risk individuals with a family history of pancreatic cancer or IPMN, PanINs may develop in large numbers, and multiple carcinomas in situ can arise simultaneously. Among these, clones exhibiting pronounced intraductal proliferation or progression toward invasion—thereby impacting clinical outcomes—may be selectively favored. This study provides novel insights into the clonal selection and molecular progression of multicentric high-grade PanINs. To our knowledge, this is the first report to comprehensively delineate the molecular trajectory of multifocal high-grade PanINs in a high-risk patient.

Introduction

The impact of underweight and obesity on clinical outcomes for intestinal Behçet’s disease (BD) is unknown. We aimed to identify the association between body mass index (BMI) and clinical outcomes in patients with intestinal BD.

Aims & Methods

We categorized 760 patients with intestinal BD according to the BMI at diagnosis into four groups (underweight, normal, overweight, obese) at Severance Hospital, Seoul, Korea between 1997 and 2021.We performed a Cox proportional hazard analysis to investigate the predictive capability of BMI for clinical outcomes such as biologics use, surgery, hospitalization and emergency room visit.

Results

Of the 760 patients, 130 patients were classified into underweight group (BMI<18.5), 384 patients into normal group (BMI 18.5~22.9), 152 patients into overweight group (BMI 23~24.9), and 94 patients into obese group (BMI≥25). Patients with a higher BMI group showed significantly lower cumulative rates of biologics use (p trend = 0.001), surgery (p trend = 0.008), hospitalization (p trend = 0.002), and emergency room visits (p trend = 0.003) than those with a lower BMI group. In a multivariate analysis, normal BMI group (HR: 0.667, 95% CI 0.483-0.992, p =0.014), overweight group (HR: 0.589, 95% CI 0.394-0.879, p=0.010), and obese group (HR: 0.515, 95% CI 0.321-0.828, p=0.006) were negatively associated with future hospitalization compared to underweight group. Overweight group (HR: 0.490, 95% CI 0.241-0.996, p =0.049) and obese group (HR: 0.312, 95% CI 0.116-0.840, p =0.021) were negatively associated with future biologics use compared to the underweight group. Normal BMI group (HR: 0.706, 95% CI 0.484-1.029, p=0.070) and obese group (HR : 0.556, 95% CI 0.303-1.020, p=0.058) were negatively associated with future surgery compared to the underweight group. Normal BMI group (HR: 0.711, 95% CI 0.513-0.985, p=0.041) and obese group (HR: 0.602, 95% CI 0.376-0.963, p=0.034) were negatively associated with future emergency room visit compared to the underweight group.

Variables		BMI
		<18.5 (n=130) Underweight	18.5~22.9 (n=384) Normal	23~24.9 (n=152) Overweight	≥25 (n=94) Obese	p value for trend
Biologics use	Event	34 (26.2%)	50 (13.1%)	21 (13.8%)	9 (9.6%)	0.001
	Multivariable-adjusteda	Reference	0.619 (0.366-1.047)*	0.490 (0.241-0.966)**	0.312 (0.116-0.840)**
Surgery	Event	45 (34.6%)	87 (22.7%)	35 (23%)	15 (16%)	0.008
	Multivariable-adjusteda	Reference	0.706 (0.484-1.029)*	0.669 (0.411-1.088)	0.556 (0.303-1.020)*
Hospitalization	Event	87 (66.9%)	194 (50.8%)	69 (45.4%)	46 (48.9%)	0.002
	Multivariable-adjusteda	Reference	0.667 (0.483-0.922)**	0.589 (0.394-0.879)**	0.515 (0.321-0.828)**
Emergency room visit	Event	71 (55%)	144 (37.6%)	61 (40.1%)	32 (34%)	0.003
	Multivariable-adjusteda	Reference	0.711 (0.513-0.985)**	0.775 (0.523-1.149)	0.602 (0.376-0.963)**

*p <0.10
**p <0.05
^aMultivariate Cox proportional hazard analysis, including the confounders such as, age, gender, medical aid, smoking, appendectomy history, family history of BD, marriage status, DAIBD score, extraintestinal manifestation, systemic BD, number of ulcers, shape of ulcers, depth of ulcers, type of ulcers, laboratory findings.

Conclusion

Underweight could affect poor outcomes in intestinal Behçet’s disease. Physicians should pay attention to the patients with underweight and make an effort to improve nutritional status.