Introduction

During endoscopic submucosal dissection (ESD) of colorectal neoplasms, an interesting feature is occasionally detected in which the muscle layer under the tumour seems to be pulled upwards into the lesion in a triangle-shape. This feature is named muscle retracting sign (MR sign) and appears to indicate a potentially difficult ESD with high risk of incomplete and non-curative resection, although data about this subject is still scarce, without current studies in western countries. The aim of this study was to evaluate whether or not MR sign is associated with worst outcomes.

Aims & Methods

A retrospective analysis, using a prospectively collected database from 2 western centres, including all patients who underwent ESD for colorectal neoplasms with positivity for MR sign from July 2017 to January 2023 was performed. The presence of MR sign was determined by the endoscopist during the procedure. The results were evaluated in terms of complete, en bloc, R0 and curative resection rates, complications and local recurrence.

Results

In a total of 411 lesions treated by ESD, 26 presented MR sign (6.3%, mean size 62,3mm, range 20-180mm): 9 colonic and 17 rectal, corresponding to 26 patients (male 61.5%, mean age 70 years): 9 in colon and 17 in rectum. Morphologically and according to Paris classification, 13 were 0-Is (50%), 10 LST-G-M (38.5%), 1 0-Isp, 1 LST-G-N and 1 LST-NG-F. Technical success was achieved in 24 lesions (24/26, 92.3%) with 2 procedures aborted due to the perception of high perforation risk, both located in the colon (2/9, 22%). In the rectum, there was the need to perform intramuscular dissection in 3 procedures to complete the resection (3/17, 17.6%). Among resected lesions, en bloc and R0 resection rates were 100% and 66.7% (16/24). According to ESGE 2022 criteria, resection was considered curative in 66.7% (16/24), non-curative with high risk in 8.3% (2/24) and with local-risk recurrence in 25% (6/24). Intraprocedure complications were recorded in 2 resections (8%), both in the rectum and both perforations endoscopically managed. No recurrence was recorded in a mean follow-up time of 7 months (range 1-22 months).

Conclusion

This analysis show that MR sign is mostly present in large bulky protruding lesions and seems associated with a higher incomplete resection procedure rate in colon lesions but in rectum. Also, it seems associated with higher complication rate, namely perforations, and non-curative resection rates among resected lesions. Therefore, in the colon, an anticipated switch for surgery in clinically fit patients should be considered in the presence of this sign or even before initiating ESD when lesion morphology suggests its presence. To the authors’ best knowledge, this is the first study of the impact of the present of MRS in ESD in the West.

References

Toyonaga T, Tanaka S, Man-I M, East J, Ono W, Nishino E, et al. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection. Endosc Int Open. 2015;3(03):E246–51.
Suzuki N, Dhillon A, Seward E, Humphries A. CLIP MUSCLE PROTECTION (CLIMP) METHOD IN MUSCLE-RETRACTING SIGN DURING COLONIC ENDOSCOPIC SUBMUCOSAL DISSECTION. Gut. 2021;70(Suppl 1):A1–A262.

Disclosure

Toyonaga T, Tanaka S, Man-I M, East J, Ono W, Nishino E, et al. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection. Endosc Int Open. 2015;3(03):E246–51.

Introduction

Pancreatic cancer (PC) screening can improve survival in high-risk patients by detecting preneoplastic lesions or early-stage tumors.
Surveillances is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, little has been described regarding the possibility of finding other morphological changes that may be also important.

Aims & Methods

The aim of the study is to evaluate all the findings described in screening test and to analyze the correlation between these two screening techniques.
Descriptive observational single-center study that includes high-risk PC patients either due to family history (familial pancreatic cancer) or because they belong to hereditary syndromes, who have been undergone pancreatic cancer screening at our center from 2015 to 2023. Demographic variables and findings described in the EUS or MRI were collected.

Results

Thirty-five patients were included, with a mean age of 57.3 ± 8.2 years and a predominance of females (65.7%). Four patients (11.4%) were smokers, two were diabetic (5.7%), and one had a history of chronic pancreatitis (2.9%). The median follow-up time was 23 months (interquartile range 8-59 months).
The most frequent hereditary syndrome was hereditary breast and ovarian cancer syndrome (n=19, 54.3%), followed by familial atypical multiple mole melanoma syndrome (n=4; 11.4%). The BRCA2 mutation was the most common identifiable genetic factor (34.8%).
Regarding screening test findings, solid tumors were detected in three patients (8.6%) (Two stage I and IV adenocarcinomas and one stage I neuroendocrine tumor). In two individuals (5.7%) branch-duct intraductal papillary mucinous neoplasm were observed. Other pancreatic abnormalities were detected in 18 patients (51.4%) that include chronic pancreatitis-like parenchymal changes (34.3%), peripancreatic lymph nodes and fatty pancreas (5.7%). Finally, in 12 patients (34.3%) the screening tests were normal.
In relation to the concordance between MRI and EUS, in ten patients (28.6%) there was no agreement between these two techniques. EUS detected more parenchymal changes (n=5), pancreatic steatosis (n=2) and one neuroendocrine tumor that were not described on MRI. In contrast, MRI detected a cystic lesion and a pseudonodular enhancement that were not found on EUS.

Conclusion

Pancreatic cancer screening in high-risk individuals, detects neoplastic and preneoplastic lesions at a high rate.
Other findings, such as chronic pancreatitis-like parenchymal changes, peripancreatic lymph nodes or fatty pancreas, were also common in these patients
MRI and EUS have a good correlation, but EUS detects more parenchymal changes.

References

1. Goggins M, Overbeek KA, Brand R et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 2020; 69 (1): 7-17
2. Bogdanski AM, van Hooft JE, Boekestijn B, Bonsing BA, Wasser MNJM, Klatte DCF, van Leerdam ME. Aspects and outcomes of surveillance for individuals at high‑risk of pancreatic cancer. Fam Cancer 2024; 23(3):323-339.
3. Blackford AL, Canto MI, Dbouk M, Hruban RH, Katona BW, Chak A et al. Pancreatic Cancer Surveillance and Survival of High-Risk Individuals. JAMA Oncol. 2024;10(8):1087-1096.
4. Maurer E, Lehman B, Matthäi E, Denzer U, Figiel J, Jseinghaus M et al. Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant‐negative familial pancreatic cancer families. United European Gastroenterol J 2024; 12 (9): 1211-1221

Clinical Case Summary

A 70-year-old patient with diabetes mellitus and cholecystectomy performed six months earlier was admitted to the emergency department for generalized abdominal pain, hyporexia and weight loss.
An abdominal CT scan showed a solid-cystic pancreatic lesion suggestive of mucinous neoplasia, together with peritoneal nodules in the right paracolic gout. In view of the suspicion of malignancy, an echoendoscopy with fine needle aspiration puncture (EUS-FNA) was performed, identifying an irregular lesion with heterogeneous and hypovascular ultrastructure in the pancreatic neck-body and a discrete dilatation of the main pancreatic duct. Finally, the histological study didn´t show neoplastic cells.
Suddenly the patient experienced a clinical worsening with severe pain and high fever. Laboratory tests showed a progressive increase in C-reactive protein and leukocytosis with left shift. In a control CT scan, a reduction in the size of the pancreatic lesion is observed, together with an increase in the peritoneal lesions which present a polyglobulated contour, hypercapillary margins and rarefaction of the surrounding fat. These finding suggesting the presence of peritoneal abscesses secondary to dropped gallstones. After broad-spectrum antibiotic therapy, the intra-abdominal abscesses improved radiologically, but the collection persisted in the right posterior pararenal space which was drained under ultrasound control with subsequent disappearance of fever and normalization of analytical parameters.
Dropped gallstones occur in approximately 7% of cholecystectomies. The secondary granulomatous reaction in paucisymptomatic patients can simulate peritoneal tumor processes in imaging tests, being one of the adverse effects described in relation to this pathology. In our case, the concomitant presence of peritoneal lesions together the pancreatic lesion oriented the initial case as a malignant process; however, the patient's evolution were key to the final diagnosis.

Introduction

In patients with chronic pancreatitis (CP), pancreatic exocrine insufficiency (PEI) and poor nutritional intake may cause nutritional deficiencies. Guidelines advise monitoring key nutrients and supplementing is case of deficiency to prevent malnutrition-related complications. However, adherence remains low, possibly due to limited evidence on the clinical relevance of single nutrient deficiencies and the benefit of targeted supplementation. The aim of this study is to evaluate the prevalence of nutritional deficiencies in patients with CP and to identify predictors of those at highest risk. Secondary, we seek to explore association between nutritional deficiencies and malnutrition-related complications, and to provide insight into the natural course of nutritional deficiencies.

Aims & Methods

We analyzed data from the COMBO-trial, a nationwide stepped-wedged cluster randomized trial to evaluate the effect of an evidence-based algorithm for the management of CP. Measurements of fat-soluble vitamins, minerals, and albumin conducted in the outpatient clinic during the 35-month study period were included. PEI was defined as fecal elastase-1 concentration <200 µg/g or the use of pancreatic enzyme replacement therapy (PERT). The Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q), designed to evaluate the severity of PEI symptoms, was administered at four distinct time points throughout the study. Supplement use was collected from health records and patient questionnaires. Multivariate logistic regression analysis was performed for the presence of multiple deficiencies. Potential predictors included patient and disease characteristics at baseline and the mean score of the PEI-Q during follow-up.

Results

In total 409 patients were included in this study. At baseline 327 (80.0%) had PEI and PERT was used by 297 (72.6%). Nutritional deficiencies were present in 195 patients (47.7%) of which 81 (19.8%) had multiple deficiencies. The prevalence of deficiencies included vitamin A in 13/172 (7.6%) patients, vitamin D 111/289 (38.4%), vitamin E 15/168 (8.9%), vitamin K 52/88 (59.1%), iron 44/137 (32.1%) calcium 4/198 (2.0%), magnesium 24/132 (18.2%) zinc 13/67 (19.4%), selenium 4/42 (9.5%), and albumin in 41/288 (14.2%) patients. No abnormal coagulation was observed in the 20 patients with vitamin K deficiency and available INR measurements. Osteopenia was diagnosed in 110/236 (46.6%) and osteoporosis in 56/236 (23.7%). Deficiencies in vitamin K and vitamin D, micronutrients critical to bone metabolism, were not associated with osteopenia or osteoporosis. Of 44 patients with an iron deficiency, 22 (50%) were anemic. Deficiency resolved without single nutrient supplementation in 71.4% (vitamin A), 75.0% (vitamin D), 50.0% (vitamin E) , 33.3% (vitamin K), 63.6% (iron), 100% (magnesium), 80.0% (zinc) of cases. Independent predictors for multiple deficiencies were more severe PEI symptoms (OR 1.86, 1.09 – 3.17) and daily alcohol consumption (OR 2.80, 1.27 – 6.18).

Conclusion

Nutritional deficiencies are present in approximately half of the patients with CP. Most nutritional deficiencies resolve without single nutrient supplementation. Predictors for multiple nutritional deficiencies were severity of PEI symptoms and daily alcohol consumption. Therefore, nutritional deficiencies should be considered a marker of malnutrition, with treatment focused on addressing the underlying cause rather than isolated correction through single nutrient supplementation.

Introduction

Despite advances with chemotherapy regimens, Pancreatic adenocarcinoma (PDAC) is becoming the 2^nd cause of cancer-related death. Personalized medicine will be the game changer, but molecular characterization of pancreatic neoplasms is yet extremely cumbersome and has been performed on surgical samples or few EUS-tissue acquisition (TA) cases, mostly for DNA analysis. Our aim was to evaluate DNA and RNA extracted for research purposes from pancreatic neoplasms employing Endoscopic Ultrasound (EUS) Fine needle aspiration (FNA) and biopsy (FNB) and adequacy to molecular analyses.

Aims & Methods

From Oct 2022, patients with solid pancreatic neoplasms suggestive of either PDAC or neuroendocrine neoplasm (NEN) undergoing diagnostic EUS-TA were considered for enrollment. Employed needles were either FNA, or Franseen, Fork-tip or Three-prong, either 22G or 25G based on operator’s preference, with Rapid on Site Evaluation and, in case of adequacy within the first 2 passes, 1 additional pass with the same needle was performed for molecular analyses. DNA and RNA were then extracted with a new technique and nucleic acids were quantified and evaluated for adequacy for molecular analysis. Mann-Whitney was employed for comparison of continuous variables, and Kruskal-Wallis test for comparison between multiple groups; Logistic regression was applied to determine factors associated with adequacy to molecular tests.

Results

351 patients underwent sampling for molecular analyses, 309 with a definitive diagnosis of PDAC and 42 with NEN. 92,9% of patients were sampled with 25G FNA needles. Median quantity of DNA extracted was significantly lower in PDAC 2048 ng (95%CI: 1470 -3651) compared to NEN 6752 ng (95%CI: 3502-9655)(p<0.0144). Mean quantity of RNA extracted was similar, 312 ng for PDAC, and 444 ng for NEN (p=0.07), with a higher median RIN of 6,4 (95%CI:6,2-6,5) for PDAC versus 4,7 (95%CI:3,9-5) for NEN (p<0.0001). In terms of needle type, concerning DNA extraction, 25G FNA needles retrieved a median of 3384 ng, 25G Franseen needles (4312 ng), 22G Franseen (73864 ng), 25G Fork-tip or Three-prong (3104 ng), with no significant difference. In terms of needle type, concerning RNA extraction, 25G FNA needles retrieved a median of 310 ng (RIN 6,3), 25G Franseen needles 460 ng (RIN 5,5), 22G Franseen 884 ng (RIN 5,9), 25G Fork-tip or Three-prong 301 ng (RIN 5,15), with no significant difference. 295 (95,5%) of PDAC samples and 34 (80,9%) of NEN samples were considered adequate for sequencing. The only factor associated to adequacy for molecular analysis was tumor type, with PDAC having an OR of 5,44 (95%CI 2,06-14,37)(p=0.0006), while the type of employed needle was not

Conclusion

Molecular analysis on EUS-acquired tissue of pancreatic neoplasms will be the mainstay of personalized therapies but how to best perform tissue acquisition and sample handling for this specific purpose is yet to be defined. This is the largest study ever performed on DNA and RNA extraction from EUS-acquired samples, demonstrating superior adequacy for molecular analysis in PDAC compared to NEN. All needle types result similar in terms of performance despite the low number of needles other than 25G FNA needles.