Intracystic Glucose Levels in Differentiating Mucinous From Nonmucinous Pancreatic Cysts: A Systematic Review and Meta-analysis.

BACKGROUND: Mucinous pancreatic cysts are well reported to transform into pancreatic adenocarcinoma, whereas nonmucinous cysts are mostly benign with low risk for malignant transformation. Nonsurgical methods of differentiating mucinous and nonmucinous pancreatic cysts are challenging and entail a multi investigational approach. Low intracystic glucose levels have been evaluated in multiple studies for its accuracy in differentiating mucinous from nonmucinous cysts of the pancreas. METHODS: Multiple databases were searched and studies that reported on the utility of intracystic glucose levels in diagnosing mucinous pancreatic cysts were analyzed. Meta-analysis was conducted using the random-effects model, heterogeneity was assessed by I2%, and pooled diagnostic test accuracy values were calculated. RESULTS: Seven studies were included in the analysis from an initial total of 375 citations. The pooled sensitivity of low glucose in differentiating mucinous pancreatic cyst was 90.5% [95% confidence interval (CI): 88.1-92.5; I2=0%] and the pooled specificity was 88% (95% CI: 80.8-92.7; I2=79%). The sensitivity at a glucose cut-off of 50 was 90.1% (95% CI: 87.2-92.5; I2=0%) and the specificity was 85.3% (95% CI: 76.8-91.1; I2=76%). The sensitivity of glucose levels in pancreatic cyst fluid taken by endoscopic ultrasound guided fine-needle aspiration was 90.8% (95% CI: 87.9-93.1; I2=0%) and the specificity was 90.5% (95% CI: 81.7-95.3; I2=83%). The sensitivity of point-of-care glucometers was 89.5% (95% CI: 87.9-93.1; I2=0%) and specificity was 83.9% (95% CI: 68.5-92.6; I2=43%). CONCLUSIONS: Low glucose level at a cut-off of 50 mg/dL on fluid samples collected by endoscopic ultrasound guided fine-needle aspiration and analyzed by point-of-care glucometer achieves excellent diagnostic accuracy in differentiating mucinous pancreatic cysts.

Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A multicenter study.

BACKGROUND AND AIM: Tissue acquisition in pancreatic cystic lesions (PCL) is the ideal method for diagnosis and risk stratification for malignancy of these lesions. Direct sampling from the walls of PCL with different devices has shown better results than cytology from cystic fluid. We carried out a retrospective, multicenter study to evaluate the feasibility, safety, and diagnostic yield of a micro-forceps, specifically designed to be used through a 19-gauge needle after endoscopic ultrasonography (EUS)-guided puncture of PCL. METHODS: We retrospectively collected data from patients who underwent EUS-through-the-needle biopsy (EUS-TTNB) in PCL at six referral centers. RESULTS: The sampling procedure was carried out in 56 patients (mean age 57.5 ± 13.1 years, M:F 17:39), and was technically successful in all of them (100%; 95% confidence interval [CI], 94-100%). Adverse events occurred in 9/56 (16.1%; 95% CI, 8-28%) patients, with self-limited intracystic hemorrhage the most common (7/56, 12.5%; 95% CI, 5-24%). All adverse events were mild, and resolved without any specific intervention. Specimens were considered adequate for histological diagnosis in 47/56 (83.9%; 95% CI, 72-92%). In two of these patients, despite the histological adequacy, a diagnosis could not be reached. In two other cases, a specimen sufficient for a cytological diagnosis was obtained. Overall diagnostic yield by combining cytological and histological samples was 47/56 (83.9%; 95% CI, 72-92%). CONCLUSION: EUS-TTNB with micro-forceps in PCL is feasible, safe, and has a high diagnostic yield. Future prospective studies are needed to better assess the clinical impact of EUS-TTNB on the management of PCL.

The real-time analysis of gastric juice (Endofaster) for detection of Helicobacter Pylori: a reliable tool in substitution of histology.

BACKGROUND: EndoFaster perform gastric juice analysis providing real-time Helicobacter pylori (HP) diagnosis during esophagogastroduodenoscopy (EGD), based on ammonium level. We aimed to assess its accuracy in detecting HP infection compared to the paired histology and to establish the optimum ammonium concentration cut-off point (COP). METHODS: Consecutive adult outpatients referred for EGD were prospectively enrolled between December 2021 and March 2022. In-patients, those with surgically altered anatomy, suspected neoplasia, and bleeding were excluded. EndoFaster and histology were performed in all patients, with additional stool antigen test (SAT) reserved for discordant cases. EndoFaster diagnostic measures were calculated, and ammonium level COP established using AUROC curve analysis. RESULTS: 101 patients (64 female, mean age 56.7±16.1 years) were included. HP infection was diagnosed in 35 (34.6%) and 15 (14.8%) patients by EndoFaster and histology, respectively. Diagnostic accuracy in comparison with histology was 77.8% (95%CI 68.3% - 85.5%). After implementing SAT for gold standard assessment, EndoFaster accuracy increased to 81.6% (95%CI 72.5%-88.7%). AUROC curve (0.93±0.03, 95%CI 0.86-0.99) identified an ammonium COP of ≥67.5ppm. Using the new COP, EndoFaster accuracy further increased to 88.8% (95%CI 80.8%-94.2%). CONCLUSIONS: Endofaster showed high accuracy for HP detection, with moderate agreement to histology. An ammonium COP of 67.5 ppm seems to be the threshold with the highest accuracy for HP detection.

Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

BACKGROUND: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m2 + 5-fluorouracil 2400 mg/m2 + leucovorin 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX) in the perioperative treatment of patients with rPDAC. METHODS: Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. RESULTS: 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. CONCLUSION: Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

Pooled diagnostic parameters of artificial intelligence in EUS image analysis of the pancreas: A descriptive quantitative review.

EUS is an important diagnostic tool in pancreatic lesions. Performance of single-center and/or single study artificial intelligence (AI) in the analysis of EUS-images of pancreatic lesions has been reported. The aim of this study was to quantitatively study the pooled rates of diagnostic performance of AI in EUS image analysis of pancreas using rigorous systematic review and meta-analysis methodology. Multiple databases were searched (from inception to December 2020) and studies that reported on the performance of AI in EUS analysis of pancreatic adenocarcinoma were selected. The random-effects model was used to calculate the pooled rates. In cases where multiple 2 × 2 contingency tables were provided for different thresholds, we assumed the data tables as independent from each other. Heterogeneity was assessed by I2% and 95% prediction intervals. Eleven studies were analyzed. The pooled overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 86% (95% confidence interval [82.8-88.6]), 90.4% (88.1-92.3), 84% (79.3-87.8), 90.2% (87.4-92.3) and 89.8% (86-92.7), respectively. On subgroup analysis, the corresponding pooled parameters in studies that used neural networks were 85.5% (80-89.8), 91.8% (87.8-94.6), 84.6% (73-91.7), 87.4% (82-91.3), and 91.4% (83.7-95.6)], respectively. Based on our meta-analysis, AI seems to perform well in the EUS-image analysis of pancreatic lesions.

Juvenile polyposis diagnosed with an integrated histological, immunohistochemical and molecular approach identifying new SMAD4 pathogenic variants.

Juvenile polyposis (JP) is a rare familial syndrome characterized by the development of numerous hamartomatous polyps of the gastrointestinal tract and by an increased risk of developing gastrointestinal cancers. It follows a pattern of autosomal dominant inheritance and is associated with germline variants of SMAD4 or BMPR1A genes. Differential diagnosis may be difficult based on histology alone, due to morphological similarities to other familial syndromes. Here we report a case of familial JP diagnosed in a 50-years woman with a familial history positive for gastrointestinal cancers and other tumor types. The patient presented with severe iron deficiency anemia and showed numerous polyps in the stomach and jejunum according to endoscopy and imaging. She underwent an intra-gastric laparoscopic removal of the major gastric polyp, followed by jejunal exploration and resection of a segment with multiple neoformations. Histological examination revealed the presence of hamartomatous polyposis. Gastric and intestinal samples were analyzed with next-generation sequencing. Molecular analysis showed that the patient harbored a germline splicing site variant of SMAD4, c.1139 + 3A > G, which was complemented by different somatic variants of the same gene in the different polyps. Immunohistochemistry for SMAD4 confirmed loss of protein expression in the polyps, with regular expression in normal cells. cDNA sequencing further confirmed the findings. We thus definitively diagnosed the woman as having JP thanks to an integrated approach based on histology, immunohistochemistry and molecular analysis. The identified variants, all previously reported as variants of unknown significance, were classified as pathogenic as they complemented each other leading to SMAD4 loss.

Ablation treatments in unresectable pancreatic cancer.

Ablation treatments have been increasingly applied as an alternative treatment for unresectable locally advanced pancreatic cancer (LAPC). The goal of LAPC therapy is surgical resection with negative margins (R0); however, that can be achieved only in a minority of patients and only following neoadjuvant treatment. Ablation might be useful for those patients with unresectable LAPC that do not progress towards metastatic stage and do not experience a true downstaging. Indeed, some LAPC that tend to grow locally, might be the subgroup of tumors that could benefit from ablation. Experience is necessary to select patients and the technique to adopt, since serious or fatal complications can occur. This review aims to discuss the role of ablation treatments in LAPC, with a unique focus on radiofrequency ablation and irreversible electroporation.

Endoscopic ultrasound-guided ethanol ablation of pancreatic neuroendocrine tumours: A case study and literature review.

Here we offer a review of the literature regarding endoscopic ultrasound-guided ethanol ablation for pancreatic neuroendocrine tumours and describe the case of a cystic tumour completely ablated after a multisession procedure. A total of 35 PubMed indexed cases of treated functioning and non-functioning pancreatic neuroendocrine tumours resulted from our search, 29 of which are well-documented and summarised. Endoscopic ultrasound-guided ethanol ablation appears as a local, minimally invasive treatment of pancreatic neuroendocrine tumours, suitable for selected patients. This technique appears feasible, relatively safe and efficient, especially when applied to symptom relief in functioning tumours, aiming at loss of endocrine secretion. For non-functioning tumours, where the goal is complete tissue ablation, eus guided ethanol ablation can provide good results for patients who are unfit for surgery or for those who refuse surgical resection. Its role in "fit for surgery" patients requires assessment through further studies.

Malignant melanoma rather than malignant cutaneous melanoma?

We report a case of an 84-year-old woman with a history of resected cutaneous melanoma who presented with asthenia, weight loss, and severe anemia. An esophagogastroduodenoscopy showed five black-pigmented submucosal tumors with large ulcerations in the antrum of the stomach and in the duodenum, suspected metastases from melanoma. Histopathological examination indicated the presence of melanin-containing tumor cells and confirmed an ulcerated pigmented melanoma. To examine the entire gastrointestinal tract, capsule endoscopy was performed and it showed a simultaneous massive involvement of the jejunum and ileum, with more than 40 lesions. This case highlights the importance of a complete endoscopic gastrointestinal examination in patients with melanoma metastatic to the bowel and suggests that capsule endoscopy is an easy, noninvasive, and effective diagnostic procedure to investigate small-bowel involvement.

Oldest biliary endoprosthesis in situ.

The advantages of endoscopic retrograde cholangiopancreatography over open surgery have made it the predominant method of treating patients with choledocholithiasis. After sphincterotomy, however, 10%-15% of common bile duct stones cannot be removed with a basket or balloon. The methods for managing "irretrievable stones" include surgery, mechanical lithotripsy, intraductal or extracorporeal shock wave lithotripsy and biliary stenting. The case presented was a referred 82-year-old Caucasian woman with a 7-year-old plastic biliary endoprosthesis in situ. To the best of our knowledge the examined endoprosthesis is the oldest endoprosthesis in situ reported in the literature. Endoscopic biliary endoprosthesis placement remains a simple and safe procedure for patients with stones that are difficult to manage by conventional endoscopic methods and for patients who are unfit for surgery or who are high surgical risks. To date no consensus has been reached regarding how long a biliary prosthesis should remain in situ. Long-term biliary stenting may have a role in selected elderly patients if stones extraction has failed because the procedure may prevent stones impaction and cholangitis.