Contrast-enhanced guided endoscopic ultrasound procedures.

Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours. Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions, further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS. This review details the knowledge based on the available data on contrast-guided procedures. The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions, which occur in select cases. Additionally, the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage, and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented. Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours, in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1ß) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1ß, glucose, and CEA, and serum for Ngal and IL-1ß. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1ß and serum Ngal made no diagnostic contribution.

New-onset Diabetes Mellitus after EUS-guided Drainage with LAMS: A Pilot Study.

BACKGROUND AND AIMS: Walled-off necrosis (WON) is a serious complication of severe pancreatitis, patients with necrotizing pancreatitis having an increased risk of developing diabetes mellitus (DM). The aim of this study was to assess the frequency of new-onset diabetes (NOD) in patients with symptomatic WON after endoscopic ultrasound (EUS)-guided drainage with lumen-apposing metal stents (LAMS). METHODS: We retrospectively analyzed a prospectively collected database of patients with symptomatic WON treated by EUS-guided drainage with LAMS in a tertiary referral center. The patients were followed-up for at least 12 months after stent removal. These patients were compared with age- and sex-matched asymptomatic WON controls without interventional treatment and healthy controls to assess the one-year occurrence of DM. Diabetes was defined according to the American Diabetes Association criteria. RESULTS: Of the 50 patients with symptomatic WON included in the study (male/female ratio, 33:17; median age, 60 years), 13 patients (26%) had pre-existing DM and were excluded. Ten of the remaining 37 patients (27%) without prior DM developed NOD within one year after stent removal, this frequency being higher than in asymptomatic WON controls (18.9%, p=0.581) and healthy controls (2%, p = 0.002). In the symptomatic WON group, NOD patients compared to non-DM patients were older (63.5 vs. 56 years old, p=0.042), had more frequent necrosis > 50% of the pancreatic parenchyma (p=0.002) and had a body-tail location of WON (p<0.001). On multivariate analysis, the number of direct endoscopic necrosectomy (DEN) sessions was the only significant factor for NOD occurrence (OR=7.05, p=0.010). NOD patients had poor glycemic control and required more DEN sessions to achieve WON resolution than patients with prior DM (p=0.017). CONCLUSIONS: In patients with symptomatic WON treated by EUS-guided drainage, DM occurred in 27% of previously non-diabetic patients within one year of follow-up. Patients with extensive pancreatic necrosis were more likely to develop NOD, a high number of DEN sessions being a significant risk factor for NOD occurrence.

Unveiling Distinct Proteomic Signatures in Complicated Crohn's Disease That Could Predict the Disease Course.

Crohn's disease (CD) is characterized by a chronic, progressive inflammation of the gastrointestinal tract often leading to complications, such as strictures and fistulae. Currently, there are no validated tools anticipating short- and long-term outcomes at an early stage. This investigation aims to elucidate variations in protein abundance across distinct CD phenotypes with the objective of uncovering potential biomarkers implicated in disease advancement. Serum samples collected from 30 CD patients and 15 healthy age-matched controls (HC) were subjected to depletion of highly abundant proteins and to a label-free mass spectrometry analysis. Twenty-four proteins were shown to be significantly different when comparing CD with HC. Of these, WD repeat-containing protein 31 (WDR31), and proteins involved in the acute inflammatory response, leucine-rich alpha-2-glycoprotein (LRG1) and serum amyloid A1 (SAA1), were more abundant in the aggressive subgroup. Against standard biomarkers, a positive correlation between SAA1 and WDR31 and C-reactive protein (CRP) was found. In this study, a unique serum biomarker panel for aggressive CD was identified, which could aid in predicting the disease course.

Anastomotic Leakage after Gastrectomy for Gastric Cancer.

Anastomotic leakage (AL) constitutes a prominent cause of significant morbidity following gastrectomy for gastric cancer. The manifestation of AL typically occurs within 7 to 10 days post-surgery, with reported incidence rates of 5.8-6.7% for open gastrectomy and 3.3-4.1% for laparoscopic gastrectomy. Various predisposing risk factors have been identified, including the individual nutritional status (excluding obesity) and preoperative corticotherapy. Interestingly, the administration of neoadjuvant therapies appears to reduce the AL occurrence. In the context of distal gastrectomies, the rates of AL are comparable between laparoscopic, robotic, and open approaches. The total gastrectomies have higher AL rate compared to distal gastrectomies, which are considered the preferred approach. Prophylactic drainage measures have not demonstrated efficacy in preventing AL. As for postoperative management, conservative treatment is indicated for patients presenting with mild clinical symptoms and increased inflammatory blood tests. This approach involves fasting, enteral or parenteral nutrition, administration of antibiotics, and percutaneous drainage. For small AL, endoscopic therapies such as stents, vacuum therapy, clips, suturing devices, and injections are appropriate treatment options. In cases of high-volume fistulas, severe sepsis or failure of previous therapies, surgical reoperation becomes the ultimate solution.

Endoscopic ultrasound drainage of pancreatic fluid collections: do we know enough about the best approach?

Pancreatic fluid collection often occurs as a local complication of acute pancreatitis, and drainage is indicated in symptomatic patients. The drainage may be surgical, percutaneous, or endoscopic ultrasound (EUS) guided. In symptomatic collections older than 4 weeks and localized in the upper abdomen, EUS-guided drainage is the first choice of treatment. Lumen-apposing metal stents are useful in cases of walled-off necrosis, facilitating access to the cavity; however, they do not reduce the number of necrosectomy sessions required. In most pancreatic pseudocysts requiring drainage, plastic stents remain the first choice of treatment. This review aimed to summarize the principles and techniques of step-up therapy of pancreatic fluid collections, including preprocedural and postprocedural assessment and practical approaches of drainage and necrosectomy, making available evidence more accessible to endoscopists aiming to train for this procedure. Successful and safe EUS drainage connotes early recognition and treatment of complications and the presence of a multidisciplinary team for optimal patient management. However, the best time for necrosectomy, modality of drainage method (lumen-apposing metal stents or plastic stents), and duration of antibiotherapy are still under evaluation.

Endoscopic ultrasound drainage of pancreatic fluid collections This review summarizes the current knowledge on the indications, techniques, outcomes, complications, and treatment-associated EUS drainage of pancreatic fluid collections. Special attention is paid to the practical approach in necrosectomy and postprocedural antibiotherapy, discontinuation of proton pump therapy, and timing of stent removal.

Endoscopic Ultrasound in the Diagnosis of Extrahepatic Cholangiocarcinoma: What Do We Know in 2023?

Extrahepatic cholangiocarcinoma (CCA) is a rare and aggressive type of cancer, presenting as a mass or as a biliary stricture. This review summarizes the utility of endoscopic ultrasound (EUS) in the detection, staging, and determination of the differential diagnosis, especially when no cause of bile duct dilatation is revealed by cross-sectional imaging. The EUS detection rate for distal CCAs is higher than that for the proximal CCAs. The accuracy of T staging varies between 60 and 80%, and vascular involvement is correctly assessed by conventional EUS. EUS-tissue acquisition from the primary tumors is reserved for unresectable or metastatic CCA, especially in distal strictures or mass CCAs. For proximal lesions, EUS could be performed as an adjunctive to ERCP sampling when the latter is inconclusive. EUS is not appropriate for assessing the malignant features of lymph nodes in CCAs. Lymph node EUS-tissue acquisition should be performed only if it changes the surgical decision. Perhaps the development of EUS-fine needle biopsy and the detection of molecular genetic alteration will increase the diagnostic yield in CCAs.

Absolute and Functional Iron Deficiency in Colon Cancer: A Cohort Study.

Background and Objectives: Iron is an essential micronutrient for many biological functions and has been found to be intimately linked to cancer biology. Although the effects of increased dietary iron consumption in the development of CRC have been previously investigated in several cohort studies, the available evidence on the involvement of iron deficiency in this process is relatively scarce. Previously published papers did not analyze specific outcomes, such as the presence of biologically aggressive histopathological characteristics, that are associated with the subtypes of iron deficiency. The purpose of this study was to investigate the connection between the development of colorectal cancer and the presence of functional iron deficiency (FID), which is defined as insufficient biological availability of iron in the presence of adequate storage reserves, or absolute iron deficiency (AID), which is defined as severely depleted iron storage levels. Materials and Methods: Our paper represents a single center registry-based cohort study. Iron levels were routinely evaluated upon diagnosis of CRC and the collected data were coupled with patient- and tumor-specific data (2018-2022). Spearman's correlation coefficient and the chi-squared test were used to analyze the association. Results: Out of 129 patients, 75 (58.13%) were anemic. AID was identified in 26.35% of cases and FID was encountered in 51.16% of cases. A statistically significant association between FID and lymphatic invasion was encountered. An analysis of the correlation demonstrated a significant association between anemia and right-sided tumor location. Conclusions: Functional iron deficiency seems to be independently associated with lymphatic invasion. Although a statistically significant correlation with the T or N stage was not demonstrated, the analysis suggested a potential positive relationship between the presence of FID and more aggressive tumor characteristics.

Clinical Utility of the Contrast-Enhanced Endoscopic Ultrasound Guided Fine Needle Aspiration in the Diagnosis of Pancreatic Cyst.

Endoscopic ultrasound fine needle aspiration (EUS-FNA) cytology from an intracystic fluid is useful in the differentiation of pancreatic cysts, with low sensitivity, which increases when the solid component is targeted. The clinical utility of contrast-enhanced guided EUS-FNA (CH-EUS-FNA) in the solid component is not known. We aimed to assess the diagnostic value of CH-EUS-FNA in enhanced mural nodules and discrimination between different cysts using contrast-enhanced endoscopic ultrasound (CH-EUS). The prospective study recruited patients with pancreatic cysts with an unclear diagnosis. The CH-EUS was followed by CH-EUS-FNA. The final diagnosis was based on surgery or the correlation between clinical history, cross-sectional imaging, echoendoscopic morphology, cystic fluid analysis, and follow-up. Fifty-eight patients with pancreatic cysts were evaluated. The mucinous cysts had wall arterial enhancement more often than non- mucinous cysts (p < 0.0001), with 90.2% sensitivity and 70.6% specificity. The CH-EUS-FNA from cystic fluid and mural nodules identified mucinous cysts and malignancy with 82.4% and 84.2% sensitivity and 92% and 100% specificity. Twenty-one cysts had solid components, but only 13 were enhanced mural nodules on EUS assessment with conclusive cytology in all cases and malignancy in 76.9%. Contrast-enhanced endoscopic ultrasound should be completed in all PCN with solid components in order to avoid unnecessary EUS-FNA and to guide FNA for the identification of malignant cysts.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy versus Fine-Needle Aspiration in the Diagnosis of Focal Liver Lesions: Prospective Head-to-Head Comparison.

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) or fine-needle aspiration (EUS-FNA) from focal liver lesions are indicated in selected cases, but there has been no previous comparison of needle types of the same size. The aim of our study was to compare the histologic diagnostic accuracy and adequacy of cores obtained with EUS-FNB needles in contrast to those obtained with FNA needles in focal liver lesions. This prospective one-center study included patients with left lobe hepatic focal lesions with contraindications for percutaneous liver biopsy or need for EUS for concomitant lesions. Each patient had one pass of 22G EUS-FNB (Franseen) needle and one pass of 22G EUS-FNA in a crossover manner, without macroscopic on-site evaluation. Each sample was analyzed separately for histologic adequacy and diagnosis. The final diagnosis was based on histology results or on imaging follow-up in the case of negative biopsies. The EUS-FNB samples (n = 30) were found to be more adequate for histologic analysis, with more cellularity and longer tissue aggregates than the EUS-FNA samples (n = 30). The accuracy of EUS-FNB was 100%, whereas that of EUS-FNA was 86.7% (p = 0.039). No post-procedure complications were noted. The 22G EUS-FNB needle proved superior to 22G EUS-FNA in terms of tissue acquisition diagnostic accuracy and histologic adequacy in focal liver lesions.

Contrast enhanced endoscopic ultrasound in the diagnosis of pancreatic metastases.

AIM: Less than 5% of pancreatic masses represent metastases and differentiation from primitive tumors using endo-scopic ultrasound (EUS) is difficult. The aim of our work was to assess the diagnostic value of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) for pancreatic metastases. MATERIAL AND METHODS: We retrospectively analyzed patients with pancreatic metastasis identified during a 8 year period in a tertiary medical center. RESULTS: We included in the study 20 patients evaluated with EUS and CH-EUS. The primary tumor was localized in the kidney (6 cases), lung (5 cases), colon (3 cases), skin (2 patients) and stomach, breast, ovary and liver (1 patient each). Only 11 patients (55%) (kidney, lung, liver, ovary or skin metastases), presented hypervascularity at EUS and arterial hyperenhancement on CH-EUS, with similar diag-nostic value. All renal metastases were hyperenhanced (the negative predictive value 100%) and the stomach, colon and ovary metastases were hypoenhanced. The fast wash-out of contrast substance was encountered in all cases or renal, pulmonary and digestive metastases, but with 53.3-64.3% specificity for the different origin of pancreatic metastases. CONCLUSIONS: The vascularity assessments on conventional EUS or CH-EUS are similar for pancreatic metastases of different origin. EUS tissue acquisition remains mandatory for the diagnosis.

Direct Comparison of Elastography Endoscopic Ultrasound Fine-Needle Aspiration and B-Mode Endoscopic Ultrasound Fine-Needle Aspiration in Diagnosing Solid Pancreatic Lesions.

Elastography endoscopic ultrasound (E-EUS) has been proved to be a valuable supplement to endoscopic ultrasound fine-needle aspiration (EUS-FNA) in differentiating solid pancreatic lesions, but the improvement of EUS-FNA guided during E-EUS has not been proven. Our study aimed to evaluate whether E-EUS fine-needle aspiration (E-EUS-FNA) was superior to B-mode EUS-FNA for the diagnosis of solid pancreatic masses and whether the diagnostic rate was affected by specific factors. Our prospective study was conducted between 2019-2020 by recruiting patients with solid pancreatic masses. E-EUS examination was followed by one pass of E-EUS-FNA towards the blue part of the lesion and a second pass of EUS-FNA. The final diagnosis was based on surgery, E-EUS-FNA or EUS-FNA results, or a 12-month follow-up. Sixty patients with solid pancreatic lesions were evaluated. The sensitivity, specificity, and accuracy for diagnosing malignancy using E-EUS-FNA and EUS-FNA were 89.5%, 100%, 90%, 93%, 100%, and 93.3%, respectively, but the differences were not significant. Neither mass location nor the lesion size influenced the results. The lengths of the core obtained during E-EUS-FNA and EUS-FNA were similar. E-EUS-FNA in solid pancreatic lesions was not superior to B-mode EUS-FNA.

Serum JAK/STAT profile is related to the IL expression but not with the outcome in pancreatic adenocarcinoma patients.

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

Serum Interleukin (IL)-23 and IL-17 Profile in Inflammatory Bowel Disease (IBD) Patients Could Differentiate between Severe and Non-Severe Disease.

Interleukin (IL)-17 and IL-23 are crucial for mediating gut mucosal inflammation in inflammatory bowel disease (IBD), which has led to new therapeutic strategies. We assessed the relevancy of IL-17 and IL-23 serum levels as potential biomarkers towards severe IBD discrimination and disease-related complications. Sixty-two patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) were included. Serum IL-17 and IL-23 were measured by sandwich enzyme-linked immunosorbent assays (ELISA). IL-23 and fecal calprotectin (FCal) were significantly higher in severe CD (p < 0.001) and UC (p < 0.001 and p = 0.001, respectively), compared to mild or moderate. Elevated C-reactive protein (CRP) was correlated with severe disease only in CD (p = 0.008), whereas for UC, disease severity was associated with increased IL-17 values (p < 0.001). Diagnostic role of IL-23 was superior to FCal in discriminating between severe and mild to moderate CD (p < 0.001). IL-23 levels were also significantly higher in CD patients with intestinal complications (p = 0.04). Both IL-17 and IL-23 correlate with IBD severity, and IL-23 might be a promising novel biomarker for severe CD. Identifying the dominant IL pathway involved in IBD severity could serve as guidance for clinical decision-making on biologic therapy.

Endoscopic ultrasonography-fine needle aspiration of solid pancreatic masses: Do we need the fourth pass? A prospective study.

BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is important for the differential diagnosis of solid pancreatic lesions. Sample adequacy is related to the number of needle passes, and European guidelines recommend three to four needle passes with a standard EUS-FNA needle. We aimed to evaluate the optimal number of passes with standard EUS-FNA needles in solid pancreatic lesions. METHODS: Patients with solid pancreatic masses without cystic component >20% on computed tomography scan, and without biliary metallic stents, or coagulation problems were included prospectively. Standard 22G needles were used (maximum four passes); each sample was paraffin-embedded and analyzed separately. Final diagnosis was established by EUS-FNA, repeat EUS-FNA, surgery, or follow-up. RESULTS: Sixty-one of 65 patients were included. The final diagnoses were adenocarcinoma (n = 44, 72%), neuroendocrine tumor (NET) (n = 10, 16%), metastasis (n = 1, 4%) and nonmalignant lesion (n = 6, 10%). Immunohistochemical staining was possible in 17 cases. The diagnosis was established by the first pass in 62% of cases (n = 38), by the second in 15% (n = 9), by the third in 15% (n = 9), and by the fourth in 3% (n = 2). The diagnostic accuracy for all four passes compared to the first three passes was 95% vs 92% (P = .5). The contribution of the fourth pass was not different between adenocarcinoma and NET (2% vs 10%, respectively; P = .667). CONCLUSION: Three passes with standard EUS-FNA was optimal for a specific diagnosis of solid pancreatic masses, regardless of the histological type of the lesion.

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.

Risk Factors in Pancreatic Adenocarcinoma: the Interrelation with Familial History and Predictive Role on Survival.

BACKGROUND AND AIMS: Pancreatic cancer is associated with poor survival and quality of life. In Romania the prognostic influence of known risk factors for pancreatic adenocarcinoma, such as age, smoking, chronic pancreatitis, diabetes mellitus, and obesity is little known. Their importance in developing cancer in families with a history of adenocarcinoma is less studied. This study aims to assess the risk factors in pancreatic ductal adenocarcinoma, in familial pancreatic adenocarcinoma, in neuroendocrine tumors and to evaluate their predictive role on survival. METHODS: We performed a prospective bicentric study of patients with pancreatic tumors detected in transabdominal imaging; we assessed the risk factors and their possible association with survival. RESULTS: 312 pancreatic cancer patients (279 with pancreatic ductal adenocarcinoma and 24 patients with neuroendocrine tumors, and nine patients with other malignant types) and 312 controls were included. The median body mass index was significantly higher in patients with neuroendocrine tumors. Positive family history for pancreatic cancer was found in 4% of patients with pancreatic cancer. The risk for familial pancreatic carcinoma was associated with the presence of new-onset diabetes (OR: 4.64, p=0.018). The multivariate logistic analysis suggested that advanced age (OR: 1.67), smoking (OR: 1.67), low body mass index (OR: 12.07), and diabetes (OR: 3.91) were risk factors for pancreatic cancer. The overall survival analysis after adjustment for age and tumor stage showed only advanced tumoral stage (HR=1.6, p=0.003) and metastasis as independent predicting factors (HR=1.67, p<0.001). CONCLUSION: Our study suggests that diabetes, smoking, underweight, and age over 60 years are risk factors for pancreatic cancer. Patients with a family history of pancreatic cancer, especially those with new-onset diabetes, should be followed carefully and considered for screening. Only an advanced tumor stage was associated with poor overall survival for patients with pancreatic ductal adenocarcinoma.

Neutrophil-to-lymphocyte ratio: a hidden gem in predicting neoadjuvant treatment response in locally advanced rectal cancer?

PURPOSE: The link between the pro-inflammatory status, tumor aggressiveness and treatment response has been well established in multiple cancers. Various hematologic and biochemical variables representing surrogates for inflammation have been used as predictive markers. Our primary aim was to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in evaluating neoadjuvant treatment response in locally advanced rectal cancer (LARC). METHODS: We included 60 consecutive patients with LARC, admitted for surgery, after completing a standard full-course neoadjuvant radio-chemotherapy regimen. NLR and other hematologic parameters were collected one day prior to surgery. Treatment response was assessed on the resection specimens. RESULTS: On univariate analysis, poor responders had a significantly higher NLR value when compared with good responders: 5.81 (5.40-7.28) vs. 3.51 (2.36-4.04), p<0.0001. NLR retained its significance on multivariate analysis, with an OR of 3.51 (1.54-6.57), p=0.001. A NLR cut-off value of 4.50 had the best predictive value for poor response, with an area under the curve (AUC) of 0.85, sensitivity of 83.3% and specificity of 83.3% (p<0.001). Other hematologic ratios, such as the derived NLR (dNLR) and platelet-to-lymphocyte ratio (PLR) were also significant predictors for poor response, although to a lesser extent when compared to NLR. CONCLUSION: NLR is a simple and cost-effective predictor for neoadjuvant treatment response in LARC. As more data is generated, clear cut-off values could provide valuable insight regarding the management of LARC.

Contrast-enhanced harmonic versus standard endoscopic ultrasound-guided fine-needle aspiration in solid pancreatic lesions: a single-center prospective randomized trial.

BACKGROUND: Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CH-EUS findings combined with EUS-guided fine-needle aspiration (EUS-FNA) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH-EUS-FNA), potentially improving the diagnostic rate of EUS-FNA, but such superiority has not been proved in prospective studies. We aimed to assess whether CH-EUS-FNA is superior to standard EUS-FNA for specific diagnosis of solid pancreatic masses and what factors affect the diagnostic rate. METHODS: This randomized controlled study in one tertiary medical academic center included patients with suspected pancreatic solid masses on transabdominal ultrasound or computed tomography (CT) scan. Two passes with a 22-G standard FNA needle were done using EUS-FNA and CH-EUS-FNA in random order, and the visible core obtained was sent for histological analysis. Final diagnosis was based on EUS-FNA or surgical specimen results and on 12-month follow-up by imaging. RESULTS: 148 patients were evaluated. EUS-FNA and CH-EUS-FNA showed diagnostic sensitivities of 85.5 % and 87.6 %, respectively (not significantly different) and the combined sensitivity of the two passes was 93.8 %. The false-negative rate was not significantly different when hypoenhanced or hyperenhanced lesions were compared with the EUS-FNA results. No differences were seen for the results related to location, size, tumor stage, chronic pancreatitis features, or presence of biliary plastic stent. CONCLUSIONS: The diagnostic rates for samples obtained using 22-G needles with standard EUS-FNA and CH-EUS-FNA were not statistically significantly different.

Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? - a systematic review.

In the 'treat-to-target' era of inflammatory bowel disease (IBD) management, small molecule drugs (SMDs) represent a promising alternative to biomolecular drugs. Moreover, increasing failure rates of anti-tumor necrosis factor α agents have contributed to the development of new molecules with different mechanisms of action and bioavailability. This review focuses on the positioning of new, orally targeted therapies in the treatment algorithm of both Crohn's disease (CD) and ulcerative colitis (UC), with special consideration to their efficacy and safety. We performed a comprehensive search of PubMed and clinical trial registries to identify randomized controlled trials assessing SMDs in adult patients with moderate-to-severe IBD, irrespective of previous exposure to other biologics. In this review, we included 15 double-blind, placebo-controlled trials that assessed the efficacy and safety of Janus kinase inhibitors, sphingosine-1-phosphate modulators (S1P), SMAD blockers, phosphodiesterase 4 inhibitors and α-4 antagonists. The primary endpoints in UC were achieved for tofacitinib in the phase III OCTAVE study and AJM-300, with a favorable safety profile. S1P receptor agonists, such as etrasimod and ozanimod, demonstrated favorable results in induction studies. For CD, filgotinib and upadacitinib also met the primary outcome criteria. Available data have demonstrated so far that SMDs have an advantageous safety and efficacy profile. However, their use in a clinical setting will eventually require a personalized, mechanism-based therapeutic approach.