Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.

Comparative Analysis of Microbial Species and Multidrug Resistance Patterns in Acute Cholangitis Patients with Cholecystectomy: A Single-Center Study.

This study aimed to compare microbial species and multidrug resistance patterns in acute cholangitis patients with and without a history of cholecystectomy, highlighting potential differences We hypothesized that post-cholecystectomy patients would exhibit distinct microbial spectra and resistance patterns. Conducted at a western Romanian hospital specializing in gastroenterology and hepatobiliary diseases from 2020 to 2023, this retrospective study included 488 acute cholangitis patients, divided into groups based on their cholecystectomy history. Bile and blood samples were analyzed for microbial identification and antibiotic susceptibility using VITEK®2. Positive biliary cultures were found in 66% of patients. The cholecystectomy group showed a higher prevalence of multidrug-resistant organisms, with 74.4% exhibiting resistance compared to 31.5% in the non-cholecystectomy group (p < 0.001). Notable microbial differences included higher occurrences of Escherichia coli (40.2%) and Enterococcus spp. (32.4%) in the cholecystectomy group. Resistance to Piperacillin/Tazobactam and Penems was significantly higher in this group, with odds ratios of 3.25 (p < 0.001) and 2.80 (p = 0.001), respectively, for the development of multidrug-resistant (MDR) bacterial species. The study confirmed our hypothesis, revealing distinct microbial profiles and a higher prevalence of multidrug resistance in acute cholangitis post-cholecystectomy patients. These findings underscore the need for tailored antibiotic strategies in managing acute cholangitis in this patient demographic.

Exceptional Liver Transplant Indications: Unveiling the Uncommon Landscape.

Liver transplantation represents the definitive intervention for various etiologies of liver failure and encompasses a spectrum of rare indications crucial to understanding the diverse landscape of end-stage liver disease, with significantly improved survival rates over the past three decades. Apart from commonly encountered liver transplant indications such as decompensated cirrhosis and liver cancer, several rare diseases can lead to transplantation. Recognition of these rare indications is essential, providing a lifeline to individuals facing complex liver disorders where conventional treatments fail. Collaborative efforts among healthcare experts lead not only to timely interventions but also to the continuous refinement of transplant protocols. This continued evolution in transplant medicine promises hope for those facing diverse and rare liver diseases, marking a paradigm shift in the landscape of liver disease management.

Considering Histologic Remission in Ulcerative Colitis as a Long-Term Target.

Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.

Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Comparative Analysis of Antibiotic Resistance in Acute Cholangitis Patients with Stent Placement and Sphincterotomy Interventions.

In response to rising concerns over multidrug resistance patterns in acute cholangitis patients, this retrospective study was conducted at the Emergency County Hospital Timisoara, Romania, encompassing patients treated between August 2020 and August 2023. The study aimed to investigate the influence of prior interventions, specifically sphincterotomy (with or without stent placement), on the current clinical and microbiological profiles of acute cholangitis patients. By differentiating between patients with a history of sphincterotomy and the endoscopic retrograde cholangiopancreatography (ERCP)-naïve, we assessed the resistance of bacterial strains to antibiotics by the Tokyo Guidelines 2018, using bile cultures from 488 patients. The study identified various multidrug-resistant organisms, with a total multidrug resistance incidence of 19.9%. Significant variations were observed in the distribution of specific microorganisms and resistance patterns across different intervention groups. Patients with previous interventions, particularly those with both sphincterotomy and stent, exhibited elevated white blood cells (WBC) and C-reactive protein (CRP) levels in comparison to their ERCP-naïve counterparts. This group also presented a striking prevalence of two bacteria in their bile cultures at 50.0%, compared to 16.1% in ERCP-naïve individuals. Regarding multidrug resistance, the prior sphincterotomy with stent placement had a prevalence of 50.0%. The presence of ESBL bacteria was also significantly higher in the same group at 28.7%, contrasting with the 8.9% in ERCP-naïve patients. Additionally, the same group had a higher burden of Klebsiella spp. infections, at 37.2%, and Enterococcus spp. at 43.6%. On the antibiotic resistance front, disparities persisted. Piperacillin/Tazobactam resistance was notably more rampant in patients with a previous sphincterotomy and stent, registering at 25.5% against 11.1% in the ERCP-naïve group. This study underscores a substantial discrepancy in multidrug resistance patterns and antibiotic resistance among acute cholangitis patients with previous manipulation of the bile ducts, without expressing significant differences by the type of stent used.

Duodenal Gangliocytic Paragangliomas-Case Series and Literature Review.

Duodenal gangliocytic paragangliomas are rare neuroendocrine tumors primarily localized in the periampullary area. Though mostly asymptomatic, they can present with various symptoms, most often jaundice, anemia and abdominal pain. The present paper is a case series report, describing our personal experience with patients presenting to the Emergency Unit with different symptoms due to duodenal gangliocytic paraganglioma. Endoscopic resection is safe and indicated in most of the cases, being also associated with lower medical costs. EUS plays a central role in the pre-resection management and in surveillance, and immunostaining is decisive to ascertain the tumor histologic origin. In addition to reporting our experience, we researched the literature regarding these rare tumors and performed a comprehensive review.

Artificial Intelligence-The Rising Star in the Field of Gastroenterology and Hepatology.

Artificial intelligence (AI) is a term that covers a multitude of techniques that are used in a manner that tries to reproduce human intelligence. AI is helpful in various medical specialties that use imaging for diagnostic purposes, and gastroenterology is no exception. In this field, AI has several applications, such as detecting and classifying polyps, detecting the malignancy in polyps, diagnosing Helicobacter pylori infection, gastritis, inflammatory bowel disease, gastric cancer, esophageal neoplasia, and pancreatic and hepatic lesions. The aim of this mini-review is to analyze the currently available studies regarding AI in the field of gastroenterology and hepatology and to discuss its main applications as well as its main limitations.

Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy: A Multicenter Experience from Romania.

Background and Objectives: Biologic therapy has fundamentally changed the opportunity of medical treatment to induce and maintain remission in inflammatory bowel disease (IBD). Nevertheless, the rate of surgery is still at a very high rate, profoundly affecting the quality of life. We aimed to analyze surgical cases at three major IBD units in order to identify the main risk factors and the impact of biologic therapy on pre- and postsurgical outcomes. Material and Methods: This was a multicenter retrospective cohort study that included 56 patients with IBD-related surgical interventions from 3 tertiary care hospitals in Bucharest, Romania. The study was conducted between January 2017 and June 2021. All data were retrospectively collected from the medical records of the patients and included the age at diagnosis, age at the time of surgery, IBD type and phenotype, biologic therapy before or/and after surgery, timing of biologic therapy initiation, extraintestinal manifestations, type of surgery (elective/emergency), early and long-term postoperative complications and a history of smoking. Results: A low rate of surgical interventions was noted in our cohort (10.3%), but half of these occurred in the first year after the IBD diagnosis. A total of 48% of the surgical interventions had been performed in an emergency setting, which seemed to be associated with a high rate of long-term postoperative complications. We found no statistically significant differences between IBD patients undergoing treatments with biologics before surgery and patients who did not receive biologics before the surgical intervention in terms of the IBD phenotype, type of surgery and postoperative complications. Conclusion: Our study showed that biologics initiated before the surgical intervention did not influence the postoperative complications. Moreover, we demonstrated that patients with Crohn's disease and no biologics were the most susceptible to having to undergo surgery. Conclusion: In conclusion, the management of patients with IBD requires a multidisciplinary approach that considers an unpredictable evolution.

Hereditary Hemorrhagic Telangiectasia-A Case Series Experience from a Liver Transplant Center in Romania.

Hereditary hemorrhagic telangiectasia (HHT) has significant morbidity due to multiorgan involvement and an unpredictable disease course. We analyzed the data of 14 patients diagnosed with HHT. The case series comprised 14 patients with a median age at presentation of 48 years old (41-74 years). In twelve patients (85.7%), the diagnosis was confirmed by using the Curacao Criteria. The most common reason for admission was epistaxis, with 9 patients (57%) presenting with nosebleed refractory to prolonged self-tamponade. The biochemical abnormalities identified were elevations in AP and gamma-GT; liver synthetic function was generally normal, even though 21% of patients had clinical or imaging findings for cirrhosis. Nosebleeds were the main reason for admission and significantly impacted quality of life through anemia and frequent hospital admissions. However, the visceral manifestations seemed to be more serious. The hepatic arteriovenous malformations (AVMs) appeared to remain asymptomatic or led to minimal changes for the majority of patients; some cases were associated with liver and biliary tract ischemia, necrosis leading to acute liver failure and even death. Hepatic AVMs can also lead to high-output heart failure due to arterio-venous shunting. The most frequent AVM was hepatic artery to hepatic vein, with secondary hepatic vein dilation and hemodynamic consequences.

Efficacy of Endobiliary Radiofrequency Ablation in Preserving Survival, Performance Status and Chemotherapy Eligibility of Patients with Unresectable Distal Cholangiocarcinoma: A Case-Control Study.

BACKGROUND: Cholangiocarcinoma is the most common malignancy of the bile ducts causing intrahepatic, hilar, or distal bile duct obstruction. Most jaundiced patients are diagnosed with unresectable tumors in need for palliative bile duct drainage and chemotherapy. Endobiliary radiofrequency ablation (RFA) is an adjuvant technique that may be applied prior to biliary stenting. The aim of our study was to assess the efficacy of endobiliary RFA prior to stent insertion in patients with unresectable distal cholangiocarcinomas. METHODS: Twenty-five patients (eight treated with RFA and stenting and 17 treated with stenting alone) were included in a case-controlled study. We prospectively assessed the impact of RFA on the survival rate, the patient performance status, and the preservation of eligibility for chemotherapy based on the patient laboratory profile. RESULTS: Patients treated with RFA prior to stenting proved to have a significantly longer survival interval (19 vs. 16 months, p = 0.04, 95% CI) and significantly better performance status. Moreover, the laboratory profiles of patients treated with RFA has been proven superior in terms of total bilirubin, liver enzymes, and kidney function, thus making patients likely eligible for palliative chemotherapy. Post-ERCP adverse events were scarce in both the study group and the control group. CONCLUSION: Given the isolated adverse events and the impact on the patient survival, performance, and laboratory profile, RFA can be considered safe and efficient in the management of patients with unresectable distal cholangiocarcinomas.

Endoscopic Management of Biliary Strictures after Orthotopic Liver Transplantation: A Single Center Experience Study.

Background and Aim. Endoscopic therapy is the method of choice in the management of biliary strictures after orthotopic liver transplantation (OLT). Even though the mainstay approach for OLT stricture complications is represented by consecutive procedures of multiple plastic stents (MPS) insertion, a valuable alternative is the use of fully covered self-expandable metal stents (FCSEMS). The aim of the study was to compare MPS with FCSEMS used in the management of OLT biliary strictures, in terms of clinical outcomes and complications. Material and Methods. This is a retrospective, single-center study conducted between February 2014 and November 2019 in the Clinical Emergency Hospital of Bucharest, Romania. We enrolled all consecutive patients who developed biliary strictures after OLT and were treated by endoscopic retrograde cholangiopancreatography (ERCP) either with MPS or FCSEMS. Results. Thirty-six patients were included in the study, 27 patients had MPS and nine patients had FCSEMS. 106 ERCP procedures were performed and 159 stents were inserted. The mean number of ERCP procedures required per patient was significantly higher for MPS than for FCSEMS (3.34 ± 1.46 vs. 2.11 ± 0.33, p < 0.001). In the FCSEMS group only one patient had three procedures, due to stent migration. Difficult cannulation was encountered in 22 patients, 18 patients from MPS group and four patients from FCSEMS group. Dilation was performed in 20 (77%) MPS patients and in four FCSEMS patients (44%). Overall, we used 159 stents for stricture resolution, 149 plastic stents and 10 FCSEMS. Mean number of stents inserted was significantly lower in the FCSEMS group compared to MPS group (1.16 ± 0.40 vs. 5.73 ± 2.64, p < 0.001). Conclusions. Stricture resolution using FCSEMS is comparable to MPS and even has some advantages. In line with prior studies, FCSEMS are effective, with fewer complications and similar outcome compared to plastic stents. Other particular aspects should be further assessed, especially long-term follow up of FCSEMS and their cost efficiency.

The Prevalence and Predictors of Restless Legs Syndrome in Patients with Liver Cirrhosis.

INTRODUCTION AND AIM: Sleep disorders are highly prevalent in patients with liver cirrhosis. The aim of this study was to investigate the prevalence of restless legs syndrome (RLS), as well as its risk factors and possible predictors, in a cohort of patients with liver cirrhosis. MATERIAL AND METHODS: We performed a cross-sectional prospective study over a period of 14 months and enrolled 69 patients with liver cirrhosis, after applying the inclusion and exclusion criteria. The cases of RLS were assessed according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria and severity scale. RESULTS: Out of the total number of patients, 55% fulfilled the criteria for RLS. Age, diabetes, severity of cirrhosis, serum creatinine, glomerular filtration rate (GFR), and mean hemoglobin were associated with the presence of RLS. Moreover, there was a significantly higher prevalence of RLS among patients with decompensated cirrhosis. From all the risk factors introduced into the multivariate analysis, only the GFR could predict the presence of RLS. CONCLUSIONS: This research shows that patients with liver cirrhosis have a high risk of RLS. Even though there are multiple risk factors associated with RLS, only the GFR could predict its occurrence in our cohort.

Endoscopic Retrograde Cholangiopancreatography in Acute Biliary Pancreatitis: Urgent vs. Delayed and the Outcome of Same-Admission Cholecystectomy.

Introduction: Acute pancreatitis (AP) represents a major burden for the medical system, associating important morbidity and mortality rates. This paper is focused on debatable aspects of the management of biliary AP, namely indications, timing and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) on the hand and, on the other hand, same-admission cholecystectomy as a preventive measure for recurrent disease. Material and methods: This is a retrospective study including 108 patients with biliary AP in whom ERCP was performed, treated in the Clinical Emergency Hospital of Bucharest between 2016 and 2020. According to the urgency of the ERCP, we divided the patients into two groups: urgent versus delayed ERCP. Results: Urgent ERCP was performed in 52 patients, while delayed ERCP was performed in 56 patients; the hospital stay was higher in the urgent group than in the delayed group (10 days vs 8 days, p = 0.299) with no difference in morbidity rates. The mean time between ERCP and surgery was 5 days, without significant difference between the groups. The laparoscopic approach was the preferred method, with a conversion rate of 7%. Conclusion: ERCP with stone extraction followed by same-admission laparoscopic cholecystectomy is a safe therapeutic option, that prevents recurrent pancreatitis. The timing of the procedures remains debatable, further prospective studies being needed to achieve statistical significance.

Impact of biliary stenting in endoscopic ultrasound-guided tissue acquisition among patients with pancreatic cancer.

INTRODUCTION: Pancreatic malignancies represent highly fatal diseases with poor prognosis and constantly increasing incidence despite modern diagnostic and therapeutic options. Both endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are regarded as mainstays in pancreatic cancer management. The present study aims to evaluate whether accuracy EUS with fine-needle aspiration or biopsy (FNA or FNB) in pancreatic cancer diagnosis is influenced by prior biliary stenting or by technical or anatomical features (stent type, number of needle passes, common bile duct or Wirsung's diameter, topographical characteristics and diameter of the pancreatic tumor). MATERIALS AND METHODS: This retrospective study includes 243 patients with pancreatic cancer who underwent ERCP and EUS with fine-needle aspiration or biopsy (FNA or FNB). RESULTS AND DISCUSSION: Out of the total number of patients, 68 were stented prior to EUS. We found that the EUS-FNA diagnostic yield is not influenced either by the presence of biliary stent, nor by the type of stent (plastic or metallic). Moreover, the mean needle passes required were similar for both stented patients and not stented ones. CONCLUSIONS: Ultimately, given our results, we can state that EUS-FNA/FNB can be safely and accurately performed in the presence of biliary stents.

A morphological and immunohistochemical study of the endoscopic ultrasound-fine-needle biopsy samples from solid pancreatic masses: a single center study.

OBJECTIVE: The purpose of this study was to present the experience of a single center on endoscopic ultrasound-fine-needle biopsy (EUS-FNB) of pancreatic solid tumors amenable to immunohistochemistry (IHC) assay. PATIENTS, MATERIALS AND METHODS: Inclusion criterion for this prospective study was identifying patients with pancreatic solid tumors, by means of imaging methods, from January 2018 to February 2020, within the Department of Gastroenterology, Emergency Clinical Hospital, Bucharest, Romania. All patients underwent EUS-FNB and the harvested tissue was sent to the Department of Pathology for histopathological (HP) diagnosis and IHC assessment if tumoral origin remained undetermined. RESULTS: A total of 57 patients were ultimately selected to take part in our study. We performed immunohistochemical analysis based on the morphological diagnosis of the pancreatic tumors and assessed cytokeratin (CK)7, CK20, caudal type homeobox 2 (CDX2), MutL homolog 1 (MLH1), MutS homolog (MSH)2, MSH6, postmeiotic segregation 2 (PMS2) for all histopathologically uncertain pancreatic ductal adenocarcinoma (PDAC) and chromogranin A, synaptophysin, pan-CK AE1∕AE3 for pancreatic neuroendocrine tumors (pNETs). Cox hazard regression was performed to identify the factors influencing the survival rate. In univariate analysis, patient survival time was significantly associated with stage, location, surgical management and CK7 positivity. Our data show a statistically significant predictive relationship between stage (regional or metastatic) and hazard for survival (p=0.015). Tumoral location in the tail (p=0.015) and radicality surgery (p=0.015) significantly decrease the survival of pancreatic cancer (PAC) patients. The presence of CK7 (p=0.015) significantly increases the survival of pancreas cancer patients. CONCLUSIONS: EUS-FNB has opened up a new path for pancreatic tumor diagnosis providing enough tissue for HP examination and IHC. A panel of several immunomarkers might aid in providing new therapies for PAC patients.

What is the Impact of the Proportion of Solid Necrotic Content on the Number of Necrosectomies during EUS-Guided Drainage using Lumen-Apposing Metallic Stents of Pancreatic Walled-off Necrosis ?

BACKGROUND AND AIMS: The fully-covered, lumen apposing metal stents are designed for one step placement, facilitating the direct endoscopic necrosectomy into the walled-off pancreatic necrosis. However, the prediction of the number of necrosectomy sessions in these patients is not known. This study evaluated the association between the proportion of solid necrotic material inside walled-off necrosis, as assessed during the endosonography placement of a lumen apposing metal stent, and the number of necrosectomies subsequently required. METHODS: Patients from three tertiary medical centers with symptomatic walled off pancreatic necrosis (pain, infection, gastric/biliary obstruction) at more than 4 weeks after onset of acute pancreatitis were retrospectively analysed. Proportion of solid necrotic debris was estimated during endosonography procedure of lumen apposing metal stents placement. Necrosectomy was performed when obstruction or inflammation occurred subsequently. Lumen apposing metal stents were removed after clearance of necrotic content. RESULTS: In 46 patients with successful lumen apposing metal stents placement, necrosectomy was performed in 39 patients (72.78%). Performance of 3 or more necrosectomies was significantly associated with more than 50% pancreatic necrosis (p=0.032), but not with walled-off pancreatic necrosis size or location. Necrotic infection during lumen apposing metal stents stenting was associated with hypoalbuminemia, but not with necrosectomy requirement. Clinical success after a median follow-up of 13.37 months was 87%. CONCLUSIONS: Walled-off pancreatic necrosis with more than 50% solid necrotic content were associated with more necrosectomy procedures, requiering longer endoscopy time, intravenous sedations, and higher costs.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer.

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. MAIN OUTCOME: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered." SECONDARY OUTCOMES: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. ANALYSIS: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. SAMPLE SIZE: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis. METHODS: Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer. RESULTS: A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55-86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07-10.54; p = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37-6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.

Anatomy of Major Duodenal Papilla Influences ERCP Outcomes and Complication Rates: A Single Center Prospective Study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been one of the most intensely studied endoscopic procedures due to its overall high complication rates when compared to other digestive endoscopy procedures. The safety and outcome of such procedures have been linked to multiple procedure- or patient-related risk factors. The aim of our study is to evaluate whether the morphology of the major duodenal papilla influences the ERCP outcomes and complication rates. METHODS: A total of 322 patients with a native papilla have been included in the study over an eight month period. Morphology of the papilla has been classified into normal papilla and four anatomical variations (Type I-IV). All patients have been prospectively monitored over a 15 day period after ERCP. Procedural outcomes and complication rates have been registered. RESULTS: Morphology of the papilla influences both overall complication rates (95%CI, p = 0.0066) and post-ERCP pancreatitis rates (95%CI, p = 0.01001) in univariate analysis. Type IV papillae have proven to be independent risk factors for post-ERCP pancreatitis in multivariate analysis (OR = 12.176, 95%CI, p = 0.005). Type I papillae have been significantly linked to difficult cannulation (AUC = 0.591, 95%CI, p = 0.008); Conclusions: In the monitored cohort morphology of the major duodenal papilla has significantly influenced both ERCP outcomes and post-procedural complication rates.