Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.

Spleen Preserving, Splenic Vessels Spearing, Pure Laparoscopic Total Duodenopancreatectomy for Intraductal Papillary Mucinous Pancreatic Neoplasia (IPMN): Case Report and Technique.

Total duodenopancreatectomy (TDP), performed exclusively by laparoscopic approach is considered one of the most complex abdominal surgical procedures. TDP with preservation of spleen vessels (operation Kimura) is a more technically-demanding procedure, but is beneficial in selected cases. While some high-volume centers have gained experience in minimally-invasive pancreatectomies, laparoscopic approach remains a recommendation for well selected patients with benign or low-grade malignant tumors and should be performed with caution, by experienced HPB surgeons. In this paper, we present a spleen preserving, splenic vessels spearing, pure laparoscopic TDP on a 40-year-old patient diagnosed with diffuse IPMN performed in our center, illustrating the operative steps.

Can the Computed Tomographic Aspect of Porto-Systemic Circulation in Cirrhotic Patients be Associated with the Presence of Variceal Hemorrhage?

Background and objectives: Variceal bleeding is a serious complication caused by portal hypertension, frequently encountered among cirrhotic patients. The purpose of this study was to determine whether the aspect of the collateral, porto-systemic circulation, as detected by CT are associated with the presence variceal hemorrhage (VH). Materials and Methods: 81 cirrhotic patients who underwent a contrast-enhanced CT examination were retrospectively included in the study. Patients were divided into two groups: Cirrhotic patients with variceal hemorrhage during the hospital admission concomitant, with the CT examination (n = 33) and group 2-cirrhotic patients, without any variceal hemorrhage in their medical history (n = 48). The diameter of the left gastric vein, the presence or absence and dimensions of oesophageal and gastric varices, paraumbilical veins and splenorenal shunts were the indicators assessed on CT. Results: The univariate analysis showed a significant association between the presence of upper GI bleeding and the diameters of paraoesophageal veins, paragastric veins and left gastric vein respectively, all of these CT parameters being higher in patients with variceal bleeding. In the multivariate logistic regression analysis, only the diameter of the left gastric vein was independently associated with the presence of variceal hemorrhage (OR = 1.6 (95% CI: 1.17-2.19), p = 0.003). We found an optimal cut-off value of 3 mm for the diameter of the left gastric vein useful to discriminate among patients with variceal hemorrhage from the ones without it, with a good diagnostic performance (AUC = 0.78, Se = 97%, Sp = 45.8%, PPV = 55.2%, NPV = 95.7%).Conclusions: Our observations point out that an objective CT quantification of porto-systemic circulation can be correlated with the presence of variceal hemorrhage and the diameter of the left gastric vein can be a reliable parameter associated with this condition.

The impact of proton pump inhibitors on bone regeneration and implant osseointegration.

Proton pump inhibitors (PPIs) have become known for the treatment of gastric-acid related disorders. Similar to any other drugs, PPIs have possible adverse reactions, being associated with bone fractures, infections, kidney disease, mineral deficiency, dementia, and pneumonia. Multiple analyses have stated that PPIs therapy may affect bone regeneration and osseointegration process, causing an increased risk of bone fracture, deterioration of bone metabolism and impaired bone healing. In this review, we emphasized the current literature regarding the influence of proton pump inhibitors in the bone regeneration process. Results from the studies suggest a link between PPIs intake and bone regeneration, but several concerns are raised regarding inadequate recipient bone, surgical trauma, limitations on the titanium surface, comorbidities or interference with other pharmacological agents. Further studies are needed to determine whether the impaired bone regeneration process is due to PPI or coexisting factors.

Intra-esophageal whitish mass - a challenging diagnosis.

BACKGROUND: Whitish intraluminal esophageal masses might represent the endoscopic feature of a bezoar or a pedunculated tumor, most likely a fibrovascular polyp, without exclusion of other mesenchymal tumors (leiomyoma, lipoma, gastrointestinal stromal tumor, leiomyosarcoma, granular cell tumor). If a process of dystrophic calcification is also encountered the differential diagnosis can be a challenge even after histological analysis, as it is highlighted by our case. CASE PRESENTATION: A 65-year-old female whom took lactate calcium tablets for 5 years presented with progressive dysphagia. A whitish esophageal mass with an appearance of a pharmacobezoar was detected at esophagoscopy. A pedunculated tumor was considered in the differential diagnosis, but the imagistic studies ruled out a pedicle. This intraluminal esophageal mass highly suggestive for a pharmacobezoar was endoscopically removed. The challenge of correct diagnosis was raised by histological examination performed after immersion into trichloracetic acid for decalcification. The identification of hyaline fibrous tissue, with numerous crystalline basophils deposits of minerals, rare fibrocytes and very few vessels brought in discussion a mesenchymal originating mass, most likely a fibrovascular polyp, even the pedicle was not detected. CONCLUSION: Based on our challenging and difficult to diagnose case we proposed an uncommon evolution: auto-amputation and calcification of an esophageal mesenchymal originating tumor (most likely a fibrovascular polyp).

How CEUS improves gallbladder pathology evaluation. A comprehensive pictorial and review of the literature.

Gallbaldder disorders represent a prevalent pathology encounterd in daily practice, both in emergency and ambulatory settings. Transabdominal ultrasound has a high accuracy for the diagnosis of gallstones and acute cholecystitis. Contrast enhanced ultrasound (CEUS) can depict and characterized the vascular pattern in cases of inflammatory or malignant processes. In an emergency situation such as acute cholecystitis in patients with comorbidities, CEUS can acurate identify a gangrenous cholecystitis; subsequently the medical management can rely on this technique. The differential diagnosis of benign vs malignant pathology, in cases of segmental or diffuse wall thickening, can also benefit from CEUS. In this paper we aimed to discuss and to illustrate the role of CEUS in gallbladder pathology.

Arterial bleeding during EUS-guided pseudocyst drainage stopped by placement of a covered self-expandable metal stent.

BACKGROUND: Hemorrhagic complications during EUS-guided pseudocyst drainage can occur, because the vessels on the internal wall of the pseudocyst might be compressed by the fluid and thus not visible on color Doppler or even power Doppler EUS. CASE PRESENTATION: We report a case of an immediate internal spurting arterial bleeding precipitated during EUS-guided pseudocyst drainage which stopped instantaneously by placement of a double flanged covered self-expandable metal stent through mechanical hemostasis. CONCLUSION: In an unusual situation of bleeding from collateral circulation near the pseudocyst wall during pseudocyst drainage, the placement of an expandable metal stent proved to be useful.

2D ultrasonography and contrast enhanced ultrasound for the evaluation of cavitating mesenteric lymph node syndrome in a patient with refractory celiac disease and enteropathy T cell lymphoma.

BACKGROUND: The cavitating mesenteric lymph node syndrome (CMLNS) is a rare manifestation of celiac disease, with an estimated mortality rate of 50%. Specific infections and malignant lymphoma may complicate its clinical course and contribute to its poor prognosis. Diagnosing the underlying cause of CMLNS can be challenging. This is the first report on contrast enhanced ultrasound (CEUS) findings in enteropathy associated T-cell lymphoma (EATL) complicating CMLNS in a gluten-free compliant patient with persistent symptoms and poor outcome. CASE PRESENTATION: We present the case of a 51-year old Caucasian male patient, diagnosed with celiac disease and CMLNS. Despite his compliance to the gluten-free diet the symptoms persisted and we eventually considered the possible development of malignancy. No mucosal changes suggestive of lymphoma were identified with capsule endoscopy. Low attenuation mesenteric lymphadenopathy, without enlarged small bowel segments were seen on computed tomography. CEUS revealed arterial rim enhancement around the necrotic mesenteric lymph nodes, without venous wash-out. No malignant cells were identified on laparoscopic mesenteric lymph nodes biopsies. The patient died due to fulminant liver failure 14 months later; the histopathological examination revealed CD3/CD30-positive atypical T-cell lymphocytes in the liver, mesenteric tissue, spleen, gastric wall, kidney, lung and bone marrow samples; no malignant cells were present in the small bowel samples. CONCLUSIONS: CEUS findings in EATL complicating CMLNS include arterial rim enhancement of the mesenteric tissue around the cavitating lymph nodes, without venous wash-out. This vascular pattern is not suggestive for neoangiogenesis, as arteriovenous shunts from malignant tissues are responsible for rapid venous wash-out of the contrast agent. CEUS failed to provide a diagnosis in this case.

The interplay between NSAIDs and Candida albicans on the gastrointestinal tract of guinea pigs.

Recent studies suggest that Candida albicans colonization is associated with several gastrointestinal inflammatory disorders and is also responsible for the delay in ulcer healing. No data are reported about the effects of C. albicans on the nonsteroidal anti-inflammatory drugs (NSAIDs)-induced necroinflammatory lesions. On the other hand, beneficial effects of NSAIDs regarding the colonization potential with C. albicans have been reported. Our aim was to investigate whether the association between NSAIDs and C. albicans could potentially induce necroinflammatory lesions in the guinea pigs gastric and enteral mucosa. Three interventional groups of 11 guinea pigs each were investigated after 5 days of receiving indomethacin, C. albicans or the association of both. C. albicans and necroinflammatory lesions were graded based on histological examinations. Statistical analysis used Mann-Whitney nonparametric test. NSAIDs did not significantly decrease C. albicans colonization grades on gastrointestinal mucosa. Administration of indomethacin subsequent to C. albicans determined significantly more severe necroinflammatory lesions compared to group that only received C. albicans. The association of NSAIDs and C. albicans did not cause significantly more severe degenerative or inflammatory lesions compared to the administration of only NSAIDs in this experimental model. Associations between NSAIDs and C. albicans caused significantly more severe necroinflammatory injuries than the lesions produced by C. albicans, without enhancing the mucosal injury or inflammation caused by NSAIDs.

An Improved Score for the Evaluation of Mucosal Healing in Inflammatory Bowel Disease-A Pilot Study.

Inflammatory bowel diseases are chronic conditions characterized by periods of remission, alternating with episodes of exacerbation, in which the primary therapeutic target is mucosal healing. Although colonoscopy is currently considered the gold standard for assessing disease activity, it presents a significant number of disadvantages. Over time, various inflammatory biomarkers have been proposed to detect disease activation, but current biomarkers have many limitations. Our study aimed to analyze the most commonly used biomarkers for patient monitoring and follow-up both independently and taken together as a group, in order to propose an improved activity score that more accurately reflects the changes occurring at the intestinal level, in order to limit the number of colonoscopic interventions. By applying logistic regression as a method of statistical analysis to the retrospectively collected data, we obtained an easy-to-calculate improved score that quantifies the chance that a given patient may be in remission or in a period of endoscopic activity. To achieve a widely accessible score that is easily accessible in clinical practice, we have included only the most commonly used clinical and biological parameters.

Emergency liver resection for non-traumatic lesions. A systematic review.

AIM: Primary liver tumors have an incidence of 20% regarding benign tumors respectively 5.7% of the overall incident cases of cancer. In any major hepatic injury, the surgical treatment has two main goals: hemostasis and excision of the affected liver segments. We aimed to systematic review the non-traumatic emergency liver resections, in order to raise concern about a rather rare, but difficult to treat hepatic pathology, which implies divergent therapeutical approach, and emergency liver surgery remains the first or backup option. METHODS: A literature survey was performed guided by the words "liver resections", "major liver resections", "emergency liver resection". "hepatocellular carcinoma" using four databases: Pubmed, Scopus, Web of Science and Embase. All titles referred in English, published from 2000 until 2021, were checked for eligibility. RESULTS: Six publications were considered relevant for major liver resections in emergency, from a total of 331 articles that were reviewed. Large hepatocellular carcinomas and adenomas were the most common types of tumors found at risk for spontaneous rupture. The patients with hemodynamic instability, reduced liver function and large tumors had lower long-term survival and disease-free survival. Major hepatectomy was indicated as a viable solution for prolonging survival rate, whenever the patient's general status permits it per primam. CONCLUSIONS: Emergency major liver resection for tumoral causes prolongs survival even if the cause is usually malignant. The tumor can be resected with negative resection margins, respecting the correct oncological requirements, both per primam or staged approach according to each case specifically. KEY WORDS: Adenoma, Emergency, Hemorrhage, Hepatocellular Carcinoma, Liver Resection, Liver Tumors.

Automated detection of celiac disease using Machine Learning Algorithms.

Celiac disease is a disorder of the immune system that mainly affects the small intestine but can also affect the skeletal system. The diagnosis relies on histological assessment of duodenal biopsies acquired by upper digestive endoscopy. Immunological tests involve collecting a blood sample to detect if the antibodies have been produced in the body. Endoscopy is invasive and histology is time-consuming. In recent years there have been various algorithms that use artificial intelligence (AI) and neural convolutions (CNN, Convolutional Neural Network) to process images from capsule endoscopy, a non-invasive endoscopy approach, that provides magnified, high qualitative images of the small bowel mucosa, to quickly establish a diagnosis. The proposed innovative approach do not use complex learning algorithms, instead it find some artefacts in the endoscopies using kernels and use classified machine learning algorithms. Each used artefacts have a psychical meaning: atrophies of the mucosa with a visible submucosal vascular pattern; the presence of cracks (depressions) that have an appearance similar to that of dry land; reduction or complete loss of folds in the duodenum; the presence of a submerged appearance at the Kerckring folds and a low number of villi. The results obtained for video capsule endoscopy images processing reveal an accuracy of 94.1% and F1 score of 94%, which is competitive with other complex algorithms. The main goal of the present research was to demonstrate that computer-aided diagnosis of celiac disease is possible even without the use of very complex algorithms, which require expensive hardware and a lot of processing time. The use of the proposed automated images processing acquired noninvasively by capsule endoscopy would be assistive in detecting the subtle presence of villous atrophy not evident by visual inspection. It may also be useful to assess the degree of improvement of celiac. Patients on a gluten-free diet, the main treatment method for stopping the autoimmune process and improving the state of the small intestinal villi. The novelty of the work is that the algorithm uses two modified filters to properly analyse the intestine wall texture. It is proved that using the right filters, the proper diagnostic can be obtained by image processing, without the use of a complicated machine learning algorithm.

Sedation for Endoscopic Retrograde Cholangiopancreatography in Elderly Patients - the Effect of Intravenous Lidocaine Infusion. A Randomised, Double-Blind, Placebo Controlled Trial.

BACKGROUND: Sedation of elderly patients with associated comorbidities, subjected to ERCP procedure, can produce serious complications including respiratory instability and hemodynamics caused by the administration of anesthetic substances. In this study we aimed to evaluate whether the administration of lidocaine in continuous infusion during ERCP procedure reduces the consumption of propofol and the rate of complications in these patients. METHODS: 83 patients over 65-year old, ASA II-IV score, undergoing an ERCP procedure were randomized in two groups: lidocaine group (group L) who received 1.5 mg/kg lidocaine 1% and propofol 1mg/kg at induction and then 2 mg/kg lidocaine 1% in continuous infusion during the procedure and control group (group C) who received saline in the same amount as group L and propofol 1mg/kg. The consumption of propofol, intraprocedural complications, the time of awakening and recovery, the quality of postprocedural analgesia, the satisfaction of the endoscopist were registered. RESULTS: Propofol consumption was statistically significantly lower in group L compared to group C [135.37 (±43.23) vs. 214.88 (±51.83), p=0.001]. The same result was obtained related to the awakening time [2.85 (±1.50) vs. 5.38 (±1.36), p=0.001] and recovery time [23.90 (±12.66) vs. 26.17 (±12.41), p<0.001], the episodes of intraprocedural desaturation (p=0.001), the involuntary intraprocedural movements (p=0.001), the endoscopist's satisfaction (p=0.006). No differences were found in terms of post-procedure pain scores (p=0.54). CONCLUSIONS: Lidocaine can be administered to reduce the need for propofol, faster awakening and lower intraprocedural complications in elderly patients undergoing the ERCP procedure.

CT-Based Radiomic Analysis May Predict Bacteriological Features of Infected Intraperitoneal Fluid Collections after Gastric Cancer Surgery.

The ability of texture analysis (TA) features to discriminate between different types of infected fluid collections, as seen on computed tomography (CT) images, has never been investigated. The study comprised forty patients who had pathological post-operative fluid collections following gastric cancer surgery and underwent CT scans. Patients were separated into six groups based on advanced microbiological analysis of the fluid: mono bacterial (n = 16)/multiple-bacterial (n = 24)/fungal (n = 14)/non-fungal (n = 26) infection and drug susceptibility tests into: multiple drug-resistance bacteria (n = 23) and non-resistant bacteria (n = 17). Dedicated software was used to extract the collections' TA parameters. The parameters obtained were used to compare fungal and non-fungal infections, mono-bacterial and multiple-bacterial infections, and multiresistant and non-resistant infections. Univariate and receiver operating characteristic analyses and the calculation of sensitivity (Se) and specificity (Sp) were used to identify the best-suited parameters for distinguishing between the selected groups. TA parameters were able to differentiate between fungal and non-fungal collections (ATeta3, p = 0.02; 55% Se, 100% Sp), mono and multiple-bacterial (CN2D6AngScMom, p = 0.03); 80% Se, 64.29% Sp) and between multiresistant and non-multiresistant collections (CN2D6Contrast, p = 0.04; 100% Se, 50% Sp). CT-based TA can statistically differentiate between different types of infected fluid collections. However, it is unclear which of the fluids' micro or macroscopic features are reflected by the texture parameters. In addition, this cohort is used as a training cohort for the imaging algorithm, with further validation cohorts being required to confirm the changes detected by the algorithm.

Hybrid Lipid Nanoformulations for Hepatoma Therapy: Sorafenib Loaded Nanoliposomes-A Preliminary Study.

Sorafenib is a multikinase inhibitor that has received increasing attention due to its high efficacy in hepatocellular carcinoma treatment. However, its poor pharmacokinetic properties (limited water solubility, rapid elimination, and metabolism) still represent major bottlenecks that need to be overcome in order to improve Sorafenib's clinical application. In this paper, we propose a nanotechnology-based hybrid formulation that has the potential to overcome these challenges: sorafenib-loaded nanoliposomes. Sorafenib molecules have been incorporated into the hydrophobic lipidic bilayer during the synthesis process of nanoliposomes using an original procedure developed in our laboratory and, to the best of our knowledge, this is the first paper reporting this type of analysis. The liposomal hybrid formulations have been characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA) that provided useful information concerning their shape, size, zeta-potential, and concentration. The therapeutic efficacy of the nanohybrids has been evaluated on a normal cell line (LX2) and two hepatocarcinoma cell lines, SK-HEP-1 and HepG2, respectively.

Laparoscopic Pancreatoduodenectomy in Elderly Patients: A Systematic Review and Meta-Analysis.

Background and Aims: Recent single-center retrospective studies have focused on laparoscopic pancreatoduodenectomy (LPD) in elderly patients, and compared the outcomes between the laparoscopic and open approaches. Our study aimed to determine the outcomes of LPD in the elderly patients, by performing a systematic review and a meta-analysis of relevant studies. Methods: A comprehensive literature review was conducted utilizing the Embase, Medline, PubMed, Scopus and Cochrane databases to identify all studies that compared laparoscopic vs. open approach for pancreatoduodenectomy (PD). Results: Five retrospective studies were included in the final analysis. Overall, 90-day mortality rates were significantly decreased after LPD in elderly patients compared with open approaches (RR = 0.56; 95%CI: 0.32−0.96; p = 0.037, I2 = 0%). The laparoscopic approach had similar mortality rate at 30-day, readmission rate in hospital, Clavien−Dindo complications, pancreatic fistula grade B/C, complete resection rate, reoperation for complications and blood loss as the open approach. Additionally, comparing with younger patients (<70 years old), no significant differences were seen in elderly cohort patients regarding mortality rate at 90 days, readmission rate to hospital, and complication rate. Conclusions: Based on our meta-analysis, we identify that LPD in elderly is a safe procedure, with significantly lower 90-day mortality rates when compared with the open approach. Our results should be considered with caution, considering the retrospective analyses of the included studies; larger prospective studies are required.

Intraoperative ultrasound in liver and pancreatic surgery.

This paper summarizes the current knowledge of intraoperative ultrasonography (IOUS) in open and laparoscopic ab-dominal surgery. The abdominal IOUS contributes to the diagnosis and staging (for parenchymal organ tumors), to establish surgical procedure and to guide surgical maneuvers. The main applications are represented by liver, biliary tract and pancreatic pathology. Diagnostic approaches are frequently combined with therapeutic purposes. The technique, equipment, training, benefits and limits of IOUS in abdominal surgery are discussed and cases from our experience are used as examples.

Desmoid tumor of the mesentery. Case report of a rare non-metastatic neoplasm.

Desmoid tumors (DT) are rare non-metastatic neoplasms that occur through myofibroblast proliferation in musculoaponeurotic or fascial structures of the body, being commonly diagnosed in young women during pregnancy or in the post-partum period. We present the case of a 38-year-old woman, who recently gave birth, manifesting non-specific abdominal symptoms. Computed tomography indicated the presence of a solitary tumor arising from the intestinal wall or from the mesentery. Surgery confirmed the diagnosis, revealing a tumor that was localized at the level of the jejunal mesentery, having about 7 cm in diameter, in tight contact with the duodenum and the mesenteric vessels. "En bloc" resection of the tumor was performed, together with the involved enteral loops followed by end-to-end anastomosis of the jejunum. Histopathological examination of the surgical specimen sustained the diagnosis of desmoid tumor.

Nanomedicine and contrast enhanced imaging. Applications in cancer diagnosis and therapy.

OBJECTIVE: Nanotechnology and its applications in medicine made us live a new era of healthcare, particularly in oncology. The objective of this paper is to review the contribution of nanotechnology in clinical use of contrast agents for gastrointestinal cancer diagnosis and follow-up and to offer an overview of the impact of nanotechnology in the management of cancer. MATERIALS AND METHODS: In this regard, we reviewed the main areas of expertise where nanotechnology has contributed to the improvement of diagnostic methods (CE-US, CE-CT, MRI), along with the therapeutic applications that nanoparticles can have. Last but not least, the article highlights the potential that theragnostic molecules can have in the diagnosis and treatment of neoplasia, including those in an advanced stage. RESULTS AND CONCLUSIONS: Nanomedicine has the ability to improve the specificity and sensitivity of cancer diagnosis, together with the enhancing of the systemic cytostatic effect by developing nano bioconjugates that have a wider effect, higher tumor selectivity and thus, lower systemic toxicity. KEY WORDS: Ablative treatment, Cancer, Contrast enhanced imaging, Drug delivery, Nanomedicine.