EUS-guided entero-colostomy with Lumen Apposing Metal Stent as a rescue treatment for malignant intestinal occlusion: a multicentre study.

BACKGROUND AND STUDY AIMS: Surgery is the first-choice treatment for malignant intestinal obstruction (MIO), however many patients are deemed unfit for surgery. Endoscopic ultrasound guided enterocolostomy (EUS-EC) with lumen apposing metal stents (LAMS) could represent a new treatment option. Primary aim was technical success of EUS-EC. Secondary aims: clinical outcome, safety, hospital stay. PATIENTS AND METHODS: Consecutive patients undergoing EUS-EC for MIO from November 2021 to September 2023 were retrospectively enrolled at four tertiary referral European centres. All cases were discussed in multidisciplinary meetings, patients declared unfit for surgery, colonic stent placement or refused surgery. RESULTS: Twelve patients were enrolled (58.3% female, median age 72.5 [42-85]). Colonic adenocarcinoma was the primary tumor in 75% of cases and 91.7% of patients had a Stage IV disease. Technical success was achieved in all procedures (100%). No LAMS misdeployment or other procedural adverse events and 3 (25%) severe post-procedural complications were observed. Clinical success was achieved in 10 (83.3%) patients, 5 (50%) resuming chemotherapy after procedure. Median post-procedural hospital stay was 9[1-20] days and overall median survival was 47.5[2-270] days. CONCLUSIONS: EUS-EC is a feasible technique and could be considered as a possible alternative to standard approaches for MIO in highly selected patients.

From sampling to cellblock: The fully automated journey of cytological specimens.

In recent years, technological innovation have emerged to standardize pathology laboratory processes and reduce the handling of diagnostic samples. Among them is an automatic tissue embedding system that eliminates the need for manual activity in tissue paraffin embedding, thereby improving sample preservation. Unfortunately, this system cannot be used for cytological specimens due to the lack of an effective holder to support the procedure steps. In this study, we evaluated the performance of a commercial polymer matrix to enable and standardize the automatic paraffin embedding of cytological material from different organs and sources. Cytological samples from 40 patients were collected on the matrices and submitted for fully automatic workflow preparation, from formalin fixation until paraffin block, using the Sakura embedding system. Our results demonstrated the feasibility of the automated procedure, from loading cytological sample onto the matrix to obtaining the paraffin cellblock, thereby avoiding manual manipulation of cellular material. All samples resulted adequately processed and paraffin-embedded showing satisfactory tissue permeation by processing reagents, optimal preservation of cytoplasmic and nuclear details, and good quality of staining results on paraffin sections. Automated embedding of cytological samples eliminates the risk of lost specimens, reduces laboratory burden, standardizes procedures, increases diagnostic yield, and ultimately improves patients' management.

Establishing the optimal number of passes during EUS-FNB for diagnosis of pancreatic solid lesions: Prospective multicenter study.

Background and study aims The optimal number of needle passes during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is not yet established. We aimed to perform a per-pass analysis of the diagnostic accuracy of EUS-FNB of solid pancreatic lesions using a 22G Franseen needle. Patients and methods Consecutive patients with solid pancreatic lesions referred to 11 Italian centers were prospectively enrolled. Three needle passes were performed; specimens were collected after each pass and processed individually as standard histology following macroscopic on-site evaluation (MOSE) by the endoscopist. The primary endpoint was diagnostic accuracy of each sequential pass. Final diagnosis was established based on surgical pathology or a clinical course of at least 6 months. Secondary endpoints were specimen adequacy, MOSE reliability, factors impacting diagnostic accuracy, and procedure-related adverse events. Results A total of 504 samples from 168 patients were evaluated. Diagnostic accuracy was 90.5% (85.0%-94.1%) after one pass and 97.6% (94.1%-99.3%) after two passes ( P =0.01). Similarly, diagnostic sensitivity and sample adequacy were significantly higher adding the second needle pass (90.2%, 84.6%-94.3% vs 97.5%, 93.8%-99.3%, P =0.009 and 91.1%, 85.7%-94.9% vs 98.2%, 95.8%-99.3%, P =0.009, one pass vs two passes, respectively). Accuracy, sensitivity, and adequacy remained the same after the third pass. The concordance between MOSE and histological evaluation was 89.9%. The number of passes was the only factor associated with accuracy. One case of mild acute pancreatitis (0.6%) was managed conservatively. Conclusions At least two passes should be performed for the diagnosis of solid pancreatic lesions. MOSE is a reliable tool to predict the histological adequacy of specimens.

Endoscopic Ultrasound-Guided Gastroenterostomy versus Enteral Stenting for Malignant Gastric Outlet Obstruction: A Retrospective Propensity Score-Matched Study.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen apposing metal stent has emerged as a minimally invasive treatment for the management of malignant gastric outlet obstruction (mGOO). We aimed to compare EUS-GE with enteral stenting (ES) for the treatment of mGOO. METHODS: Patients who underwent EUS-GE or ES for mGOO between June 2017 and June 2023 at two Italian centers were retrospectively identified. The primary outcome was stent dysfunction. Secondary outcomes included technical success, clinical failure, safety, and hospital length of stay. A propensity score-matching analysis was performed using multiple covariates. RESULTS: Overall, 198 patients were included (66 EUS-GE and 132 ES). The stent dysfunction rate was 3.1% and 16.9% following EUS-GE and ES, respectively (p = 0.004). Using propensity score-matching, 45 patients were allocated to each group. The technical success rate was 100% for both groups. Stent dysfunction was higher in the ES group compared with the EUS-GE group (20% versus 4.4%, respectively; p = 0.022) without differences in clinical efficacy (p = 0.266) and safety (p = 0.085). A significantly shorter hospital stay was associated with EUS-GE compared with ES (7.5 ± 4.9 days vs. 12.5 ± 13.0 days, respectively; p = 0.018). Kaplan-Meier analyses confirmed a higher stent dysfunction-free survival rate after EUS-GE compared with ES (log-rank test; p = 0.05). CONCLUSION: EUS-GE offers lower rates of stent dysfunction, longer stent patency, and shorter hospital stay compared with ES.

Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.

Optimization of laser dosimetry based on patient-specific anatomical models for the ablation of pancreatic ductal adenocarcinoma tumor.

Laser-induced thermotherapy has shown promising potential for the treatment of unresectable primary pancreatic ductal adenocarcinoma tumors. Nevertheless, heterogeneous tumor environment and complex thermal interaction phenomena that are established under hyperthermic conditions can lead to under/over estimation of laser thermotherapy efficacy. Using numerical modeling, this paper presents an optimized laser setting for Nd:YAG laser delivered by a bare optical fiber (300 µm in diameter) at 1064 nm working in continuous mode within a power range of 2-10 W. For the thermal analysis, patient-specific 3D models were used, consisting of tumors in different portions of the pancreas. The optimized laser power and time for ablating the tumor completely and producing thermal toxic effects on the possible residual tumor cells beyond the tumor margins were found to be 5 W for 550 s, 7 W for 550 s, and 8 W for 550 s for the pancreatic tail, body, and head tumors, respectively. Based on the results, during the laser irradiation at the optimized doses, thermal injury was not evident either in the 15 mm lateral distances from the optical fiber or in the nearby healthy organs. The present computational-based predictions are also in line with the previous ex vivo and in vivo studies, hence, they can assist in the estimation of the therapeutic outcome of laser ablation for pancreatic neoplasms prior to clinical trials.

EUS-guided gastroenterostomy using a novel electrocautery lumen apposing metal stent for treatment of gastric outlet obstruction (with video).

BACKGROUND AND AIM: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) for the treatment of gastric outlet obstruction (GOO) has been actually performed only with one type of electrocautery lumen-apposing metal stents (EC-LAMS). We aimed to evaluate the safety, technical and clinical effectiveness of EUS-GE using a newly available EC-LAMS in patients with malignant and benign GOO. MATERIALS AND METHODS: Consecutive patients who underwent EUS-GE for GOO using the new EC-LAMS at five endoscopic referral centers were retrospectively evaluated. Clinical efficacy was determined utilizing the Gastric Outlet Obstruction Scoring System (GOOSS). RESULTS: Twenty-five patients (64% male, mean age 68.7 ± 9.3 years) met the inclusion criteria; 21 (84%) had malignant etiology. Technically, EUS-GE was successful in all patients, with a mean procedural time of 35 ± 5 min. Clinical success was 68% at 7 days and 100% at 30 days. The mean time to resume oral diet was 11.4 ± 5.8 h, with an improvement of at least one point of GOOSS score observed in all patients. The median hospital stay was 4 days. No procedure-related adverse events occurred. After a mean follow-up of 7.6 months (95% CI 4.6-9.2), no stent dysfunctions were observed. CONCLUSION: This study suggests EUS-GE can be performed safely and successfully using the new EC-LAMS. Future large multicenter prospective studies are needed to confirm our preliminary data.

Fluorescence confocal microscopy for rapid evaluation of EUS fine-needle biopsy in pancreatic solid lesions.

Video 1EUS fine-needle biopsy of a pancreatic solid lesion evaluated with fluorescence confocal microscopy.

Endoscopic ultrasound-guided fine-needle biopsy with or without macroscopic on-site evaluation: a randomized controlled noninferiority trial.

BACKGROUND : The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. METHODS : This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. RESULTS : 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %-93.9 %] vs. 87.8 % [95 %CI 82.1 %-92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %-96.3 %] vs. 95.5 % [95 %CI 91.4 %-98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P < 0.001). CONCLUSIONS : The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.

New digital confocal laser microscopy may boost real-time evaluation of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from solid pancreatic lesions: Data from an international multicenter study.

BACKGROUND: Pancreatic cancer is an aggressive malignancy and a leading cause of cancer death worldwide; its lethality is partly linked to the difficulty of early diagnosis. Modern devices for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) were recently developed to improve targeting and sampling of small lesions, but innovative technologies for microscopic assessment are still lacking. Ex vivo fluorescence confocal laser microscopy (FCM) is a new digital tool for real-time microscopic assessment of fresh unfixed biological specimens, avoiding conventional histological slide preparation and potentially being highly appealing for EUS-FNB specimens. METHODS: This study evaluated the possible role of FCM for immediate evaluation of pancreatic specimens from EUS-FNB. It involved comparison of the interobserver agreement between the new method and standard histological analysis during international multicenter sharing of digital images. Digital images from 25 cases of EUS-FNB obtained with real-time FCM technology and 25 paired digital whole-slide images from permanent conventional paraffin sections were observed by 10 pathologists from different Institutions in Europe, Japan, and the United States, in a blinded manner. The study evaluated 500 observations regarding adequacy, morphological clues, diagnostic categories, and final diagnosis. FINDINGS: Statistical analysis showed substantial equivalence in the interobserver agreement among pathologists using the two techniques. There was also good inter-test agreement in determining sample adequacy and when assigning a diagnostic category. Among morphological features, nuclear enlargement was the most reproducible clue, with very good inter-test agreement. INTERPRETATION: Findings in this study are from international multicenter digital sharing and are published here for the first time. Considering the advantages of FCM digital diagnostics in terms of reduced time and unaltered sample maintenance, the ex vivo confocal laser microscopy may effectively improve traditional EUS-FNB diagnostics, with significant implications for planning modern diagnostic workflow for pancreatic tumors. FUNDING: This study was not supported by any funding source.

Predictors of adverse events after endoscopic ultrasound-guided through-the-needle biopsy of pancreatic cysts: a recursive partitioning analysis.

BACKGROUND AND STUDY AIMS : Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). PATIENTS AND METHODS : Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. RESULTS : Mean cysts size was 36.7 mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45 %), serous cystadenoma (18.8 %), and mucinous cystadenoma (12.8 %). Fifty-eight (11.5 %) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09-2.14; p = 0.05), number of TTNB passes (OR from 2.17, 1.32-4.34 to OR 3.16, 2.03-6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31-0.95; p = 0.02), and diagnosis of IPMN (OR 4.16, 2.27-7.69; p < 0.001) were found to be independent predictors of AEs, as confirmed by logistic regression and random forest analyses. RPA identified three risk classes: high-risk (IPMN sampled with multiple microforceps passes, 28 % AEs rate), low-risk (1.4 % AE rate, including patients < 64 years with other-than-IPMN diagnosis sampled with ≤ 2 microforceps passes and with complete aspiration of the cyst) and middle-risk class (6.1 % AEs rate, including the remaining patients). CONCLUSION : TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

A new micro-forceps for endoscopic ultrasound-guided through-the-needle biopsy in the diagnosis of pancreatic cystic lesions: Single center experience.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) has improved the diagnostic algorithm of pancreatic cystic neoplasms (PCNs). Recently, a new through-the-needle micro-forceps device (Micro Bite, MTW Endoskopie Manufakture) has been introduced. The primary aim was to assess the safety and technical success of this new type of micro-forceps. The secondary aim was to evaluate the diagnostic role of EUS-TTNB. METHODS: Retrospective study of consecutive patients receiving EUS-TTNB for the diagnosis of PCNs. Two micro-forceps were used: Moray Micro-forceps and Micro-Bite. Cystic fluid was collected for cytological analysis. Categorical variables were analyzed by Fisher's exact test, and continuous variables were analyzed by Student's t-test. P < 0.05 was considered significant. RESULTS: Forty-nine patients enrolled in the study (24% male; mean age 63 ± 14 years). TTNB was successfully performed in all patients. A diagnostic sample was obtained in 67.3% PCNs with TTNB compared with 36.7% with cyst fluid cytology (P 0.01). Adverse events rate was 10.2% and occurred in older patients (76.6 ± 5.4 vs 61.3 ± 13.7 P = 0.02). The 51% underwent EUS-TTNB with Micro Bite. A diagnostic sample was obtained in 52% PCNs with Micro Bite compared with 24% obtained with cyst fluid cytology (P = 0.07). Comparing the two devices, the rate of diagnostic sample obtained with the micro-forceps Moray was higher than that obtained with the Micro Bite (20/24 [83.3%] vs 13/25 [52%] P 0.03). CONCLUSIONS: EUS-TTNB increases the diagnostic yield of PCNs. The new Micro-Bite could represent a valid alternative to the currently used Moray Micro-forceps, but its diagnostic rate is still suboptimal and further studies are needed.

Role of fluorescence confocal microscopy for rapid evaluation of EUS fine-needle biopsy sampling in pancreatic solid lesions.

BACKGROUND AND AIMS: EUS fine-needle biopsy (EUS-FNB) sampling is the standard procedure for diagnosis of pancreatic lesions. Fluorescence confocal microscopy (FCM) allows imaging of tissues in the fresh state, requiring minimal preparation without damage or loss of tissue. Until now, no data exist on FCM in the field of microhistologic specimens. We aimed to assess the diagnostic performance of FCM in predicting histologic adequacy of EUS-FNB samples in pancreatic solid lesions and to assess the agreement between FCM evaluation and final histology. METHODS: In this single-center prospective study on consecutive patients with pancreatic lesions receiving EUS-FNB, the obtained samples have been evaluated at FCM and classified as "inadequate" or "adequate" (benign, suspicious, or malignant). The kappa test was used to quantify agreement. The diagnostic accuracy of FCM was assessed. A P < .05 was considered to be statistically significant. RESULTS: From April 2020 to September 2020, 81 patients were enrolled. In all cases FCM showed the macro image of the sample and created a digital image. Of the samples, 92.6% was defined as adequate at the FCM evaluation and confirmed at histopathology. Histologic diagnoses were 8% benign, 17.3% atypical/suspicious, and 74.7% malignant with satisfactory agreement with the FCM evaluation (Cohen's κ coefficient, .95; 95% confidence interval [CI], .89-1.01; P = .001). The sensitivity of the FCM evaluation was 100% (95% CI, 95%-100%), specificity 66.7% (95% CI, 22.3%-95.7%), accuracy 97% (95% CI, 90.7%-99.7%), positive predictive value 97% (95% CI, 91.8%-99%), and negative predictive value 100%. CONCLUSIONS: FCM represents a new technique successfully applicable to microhistologic specimens. It provides fast information about sample adequacy in small specimens with good agreement in the final histology.

Accuracy of visual on-site evaluation (Vose) In predicting the adequacy of Eus-guided fine needle biopsy: A single center prospective study.

OBJECTIVE: Endoscopic ultrasound is the standard procedure for the diagnosis of pancreatic lesions and new needles have been developed to improve tissue acquisition (FNB). Rapid onset evaluation (ROSE) decreases the number of needle passes but is not always available. We introduced an easy and rapid method of direct classification of EUS-FNB sample namely Visual on-site evaluation (VOSE). AIMS: To assess the accuracy of VOSE in predicting the histological adequacy of specimens. To evaluate the diagnostic power of FNB and the rate of core tissue obtained. METHODS: Prospective single center study on patients with pancreatic lesions that underwent EUS-FNB. VOSE parameters were presence of blood, macroscopic visible core (MVC), number, color and length of specimen. The association between VOSE tool and histological adequacy was assessed. Fisher's exact test and Student's t-test used to compare categorical and continuous variables. Logistic regression analysis was used to assess association between variables. RESULTS: 99 patients (58.6% male; mean age 68.4 ± 10) enrolled, including 102 lesions. Total number of passes was 358 with median number of 4 (range, 2-4). The 92.7% of samples were adequate and it was higher with the 22-G needle than with 25G (96.5% vs 89.2% p 0.01). VOSE "red-mixed specimen" was associated with a higher probability of histological adequacy (OR 2.39 95% CI 1.03-5.42 p = 0.04). CONCLUSIONS: The VOSE tool "red-mixed specimen" can be used to predict the histological adequacy and guide the number of needle passes. Overall, FNB provides a high rate of adequate and diagnostic specimen and high rate of core tissue especially with the 22G needle.

Gynecological and reproductive factors and the risk of pancreatic cancer: A case-control study.

BACKGROUND: /Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women. METHODS: We conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher's exact tests where appropriate for categorical variables and Student's t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders. RESULTS: 253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91-0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30-0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15-0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38-0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC. CONCLUSIONS: These data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.