Targeted transcriptomic analysis of pancreatic adenocarcinoma in EUS-FNA samples by NanoString technology.

Background: Integration of transcriptomic testing into EUS-FNA samples is a growing need for precision oncology in pancreatic ductal adenocarcinoma (PDAC). The NanoString platform is suitable for transcriptome profiling in low yield RNA samples. Methods: Inclusion of patients that underwent EUS-FNA cytological diagnosis of pancreatic ductal adenocarcinoma using 19G and/or 22G needles and subsequent surgical resection. Formalin-fixed, paraffin-embedded (FFPE) cytological and surgical samples underwent RNA extraction and transcriptomic analysis using a custom 52-gene NanoString panel of stromal PDAC features. Cell type abundance was quantified in FFPE specimens and correlated. Results: 18 PDAC patients were included. Mean EUS-FNA passes was 2 + 0.7. All FFPE passed the RNA quality control for genomic analysis. Hierarchical clustering on the global gene expression data showed that genes were differentially expressed between EUS and surgical samples. A more enriched cancer-associated fibroblasts and epithelial-mesenchymal transition transcriptomic profile was observed across surgical specimens whereas immunological biomarkers were more represented in EUS-FNA samples. Cytological examination confirmed a scanty representation of CAF and more immunological cell abundance in cytological samples in comparison to surgical specimens. Conclusion: Targeted transcriptomic NanoString profiling of PDAC samples obtained by EUS-FNA is a feasible approach for pre-surgical molecular analysis although stromal CAF/EMT mRNA biomarkers are underrepresented.

Safety and efficacy of endoscopic vacuum therapy for the treatment of perforations and anastomotic leaks of the upper gastrointestinal tract. / Eficacia y seguridad de la terapia de vacío endoscópica para el tratamiento de perforaciones y dehiscencias anastomóticas del tracto digestivo superior.

AIM: To evaluate the efficacy and safety of endoscopic vacuum therapy (EVT) in the management of perforations and anastomotic leaks of the upper gastrointestinal tract. PATIENTS AND METHODS: This is a retrospective observational study which included patients who underwent EVT due to any upper gastrointestinal defect between April 2017 and February 2019 in three Spanish Hospitals. To this end, we used the only medical device approved to date for endoscopic use (Eso-SPONGEr; B. Braun Melsungen AG, Melsungen, Germany). RESULTS: 11 patients were referred for EVT of an anastomotic leak after esophagectomy (n=7), gastrectomy (n=2), esophageal perforation secondary to endoscopic Zenker's septomiotomy (n=1) and Boerhaave syndrome (n=1). The median size of the cavity was 8×3cm. The median delay between surgery and EVT was 7 days. The median of EVT duration was 28 days. The median number of sponges used was 7 and the mean period replacement was 3.7 days. In 10 cases (91%), the defect was successfully closed. In 9 cases (82%) clinical resolution of the septic condition was achieved. 5 patients presented some adverse event: 3 anastomotic strictures, 1 retropharyngeal pain and 1 case of new-onset pneumonia. The median hospital stay from the start of EVT was 45 days. 1 patient died owing to septic complications secondary to the anastomotic leak. CONCLUSION: EVT was successful in over 90% of perforations and anastomotic leaks of the upper gastrointestinal tract. Moreover, this is a safe therapy with only mild adverse events associated.

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

Endoscopic ultrasound-guided fine-needle aspiration and trucut biopsy in the diagnosis of gastric stromal tumors: a randomized crossover study.

BACKGROUND AND AIM: The diagnosis of gastrointestinal stromal tumors (GISTs) has important prognostic and therapeutic implications. The specific diagnosis of GIST has to be based on immunocytochemistry. This study aimed to prospectively compare in a crossover manner the accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB) in the specific diagnosis of gastric GISTs. We hypothesized that EUS-TCB is superior to EUS-FNA in this respect. PATIENTS AND METHODS: Forty patients with gastric subepithelial tumors suspected on the basis of EUS of being a GIST underwent both EUS-FNA and EUS-TCB. The sequence in which the techniques were employed was randomly assigned to avoid bias. RESULTS: Forty tumors were sampled (mean number of passes: 2.1 +/- 0.9 with EUS-TNB and 1.9 +/- 0.8 with EUS-FNA; P = not significant, NS). Final diagnoses were: GIST (n = 27), carcinoma (n = 2), leiomyoma (n = 1), schwannoma (n = 1), and no diagnosis possible (n = 9). Device failure occurred in 6 patients with EUS-TCB. A cytohistological diagnosis of mesenchymal tumor (n = 29) and carcinoma (n = 2) was made in 70 % of cases by EUS-FNA and in 60 % of cases by EUS-TCB ( P = NS). Among the samples that were adequate, immunohistochemistry could be performed in 74 % of EUS-FNA samples and in 91 % of EUS-TCB samples ( P = 0.025). When inadequate samples were included, the overall diagnostic accuracy of EUS-FNA was 52 % and that of EUS-TCB was 55 % ( P = NS). There were no complications. CONCLUSIONS: EUS-TCB is not superior to EUS-FNA in GISTs because of the high rate of technical failure of trucut. However, when an adequate sample is obtained with EUS-TCB, immunohistochemical phenotyping is almost always possible. EUS-TCB can be safely performed in this set of patients.

Severe complications limit long-term clinical success of self-expanding metal stents in patients with obstructive colorectal cancer.

OBJECTIVES: Self-expanding metal stents (SEMS) are increasingly being used to treat malignant colorectal obstruction. However, complications have been reported in up to 50% of patients. There is limited information on long-term outcomes of these patients. The aim of this study was to retrospectively assess the long-term clinical success of SEMS in patients with malignant colorectal obstruction in a single tertiary center and to identify possible predictive factors of developing complications. METHODS: A total of 47 attempts to insert colorectal SEMS were made in 47 patients during a 5-year period. Stents of 9-cm length were placed under endoscopic and radiologic monitoring. After 24 h, all patients underwent abdominal X-ray to verify correct positioning of the stent. Patients were followed at the outpatient clinic. RESULTS: Insertion success was achieved in 44 (94%) patients. Acceptable initial colonic decompression was observed in 44 out of 47 (94%) attempts and in all (100%) successfully inserted stents. The stents were placed in the rectum (n=7, 15%), sigmoid (n=33, 70%), left colon (n=4, 9%), or anastomosis (n=3, 6%). The majority of patients had stage IV disease (n=40, 85%). SEMS served as a bridge to scheduled surgery in 9 (20%) patients and as a palliative definitive treatment in 38 (80%) cases. Three patients were lost to follow-up, so the outcome was evaluated in 41 patients. Long-term clinical failure occurred in 21 (51%) patients and was due to complications such as: migration (n=9, 22%), obstruction (n=7, 17%), perforation (n=3, 7%), and tenesmus (n=2, 5%). Perforations occurred 3, 4, and 34 days after insertion, and all patients died. In the bridge-to-surgery group, primary anastomosis was possible in only four of nine patients (44%). Clinical failure was not associated with any tumor-related factor. However, eight of nine patients with stent migration and two of three patients with perforation had been previously treated with chemotherapy. CONCLUSIONS: Placement of SEMS does not seem to be as effective as suggested because of late complications. For patients with potentially curable lesions, the use of colonic stents for malignant obstruction should only be considered when surgery is scheduled shortly after the stent insertion. Moreover, in patients with incurable obstructing colorectal cancer eligible for chemotherapy and a long life expectancy, palliative treatments other than SEMS should be considered.

Incidence and clinical significance of hyperamylasemia after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions: a prospective and controlled study.

BACKGROUND AND STUDY AIM: Acute pancreatitis as a complication of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions is rarely observed. However, there is little information on the incidence of hyperamylasemia after EUS-FNA of the pancreas and its clinical significance. This study aimed to supply this lack of information. PATIENTS AND METHODS: Patients who underwent EUS-FNA of a pancreatic lesion between October 2004 and October 2005 were studied prospectively. Exclusion criteria were: (i) platelet count under 50,000/mm (3) and/or prothrombin time < 50 %; (ii) performance of surgery, endoscopic retrograde cholangiopancreatography (ERCP), a percutaneous biopsy attempt, or another invasive procedure within 7 days before EUS-FNA; (iii) lack of informed consent. Serum amylase levels were determined before and 8 and 24 h after the procedure. Hyperamylasemia was defined by amylase levels above 104 UI/L (and higher than baseline levels) 8 h after the procedure. Acute pancreatitis was defined by upper abdominal pain (with or without nausea and/or vomiting) accompanied by elevation of serum amylase or lipase to at least twice baseline levels. RESULTS: A total of 100 patients underwent EUS-FNA of a pancreatic lesion (58 men, 42 women; mean age 60 +/- 13 years). Eleven patients (11 %) showed hyperamylasemia 8 h after the puncture (298 +/- 293 UI/L, range 105 - 1044 UI/L), but only two of them developed acute mild pancreatitis after EUS-FNA. Hyperamylasemia was not related either to the type of lesion (cystic or solid) or to its location, the duration of the procedure, or the number of passes performed. CONCLUSIONS: Pancreatitis after pancreatic EUS-FNA occurs in 2 % of patients, with some more cases of silent hyperamylasemia. This complication may have to be included in the information given to patients for their informed consent.