Outcome of probe-based confocal laser endomicroscopy (pCLE) during endoscopic retrograde cholangiopancreatography: a single-center prospective study in 45 patients

Background: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC). Aims: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP). Methods: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year. Results: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred. Conclusions: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer

Tissue microarray-chip featuring computerized immunophenotypical characterization more accurately subtypes ampullary adenocarcinoma than routine histology

BACKGROUND Ampullary adenocarcinomas (AACs) are heterogeneous tumors currently classified into three important sub-classes (SC): Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent. However, they respond differently to chemotherapy and have different prognostic outcomes. The SC are often difficult to identify with conventional histology alone. The clinical outcome of all three remains unclear, particularly for MT. AIM To identify two main subtypes of AACs, using an immunohistochemical (IHC) score based on CDX2, CK7 and CK20. METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2, CK7 and CK 20. An IHC score was obtained for each marker by counting the number of positive cells (0 = no stained cells; 1 < 25%; 2 < 50% and 3 > 50%) and their intensity (1 = weak; 2 = moderate and 3 = strong). A global score (GS) was then obtained by summation of the IHC scores of each marker. The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype, obtaining only two AACs subtypes. The overall survival in INT and PB patients was obtained by Kaplan-Meier methods. RESULTS Histological parameters defined the AACs subtypes as follows: 15% INT, 45% PB and 40% MT. Using IHC expression and the GS, 75% and 25% of MT samples were assigned to either the INT or the PB group. The mean value of the GS was 9.5 (range 4-16). All INT samples had a GS above the average, distinct from the PB samples which had a GS score significantly below the average (P = 0.0011). The INT samples were identified by high expression of CDX2 and CK20, whereas PB samples exhibited high expression of CK7 and no expression of CK20 (P = 0.0008). The INT group had a statistically significant higher overall survival than in the PB group (85.7 mo vs 20.3 mo, HR: 8.39; 95%CI: 1.38 to 18.90; P = 0.0152). CONCLUSION The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes, which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies

Preoperative biliary drainage by plastic or self-expandable metal stents in patients with periampullary tumors: results of a randomized clinical study

Background and study aims Preoperative biliary drainage in patients with periampullary tumors and jaundice has been popularized to improve the quality of life and minimize the risks associated with subsequent radical surgery. The aim of this study was to investigate the possible superiority of self-expandable metal stents (SEMS) over plastic stents, by comparing the amount of bacteria in intraoperatively collected bile and using this variable as a proxy for the efficacy of the respective biliary drainage modalities. Patients and methods In this randomized clinical trial, 92 patients with obstructive jaundice were enrolled; 45 were allocated to the plastic stent group and 47 to the SEMS group. The primary outcome was the extent and magnitude of biliary bacterial growth at the time of surgical exploration. Secondary outcomes were: macroscopic grading of inflammation of the stented bile ducts, occurrence of adverse events after stenting, stent dysfunction, recognized surgical complexities, and incidence of postoperative complications. Results The patients were well matched regarding clinical and disease-specific characteristics. At surgery, there were no group differences in the bacterial amount and composition of the bile cultures or the perceived difficulty of surgical dissection. During the preoperative biliary drainage period, more instances of stent dysfunction requiring stent replacement were recorded in the plastic stent group (19 % vs. 0 %; P = 0.03). Postoperative complications in patients who underwent curative surgery were more common in patients with plastic stents (72 % vs. 52 %), among which clinically significant leakage from the pancreatic anastomoses seemed to predominate (12 % vs. 3.7 %); however, none of these differences in postoperative adverse events reached statistical significance. Conclusion This randomized clinical study was unable to demonstrate any superiority of SEMS in the efficacy of preoperative bile drainage, as assessed by the amount of bacteria in the intraoperatively collected bile. However, some data in favor of SEMS were observed among the clinical secondary outcomes variables (preoperative stent exchange rates) without increases in local inflammatory reactions

Global Survey on Pancreatic Surgery During the COVID-19 Pandemic

This global survey among members of seven international pancreatic associations and study groups elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58\u2005years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40\u2005mm (2-200)), 9% had resection beyond 1\u2005year of follow-up (3\u2005years (1-20), size at diagnosis: 25\u2005mm (4-140)) and 39% had no surgery (3.6\u2005years (1-23), 25.5\u2005mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1\u2005year (n=1271), size increased in 37% (growth rate: 4\u2005mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN

European evidence-based guidelines on pancreatic cystic neoplasms

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring = 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN

Evidence Map of Pancreatic Surgery–A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS)

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30, 860 articles reviewed, 328 randomized controlled trials on 35, 600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%–1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%–61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%–80%) for distal pancreatectomy. Conclusion: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers. © 2021 The Author