Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.

BACKGROUND AND AIMS: Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial. METHODS: A vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety. RESULTS: There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean ±â€…SD: -86.2 ±â€…92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 ±â€…4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 ±â€…1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-γ [46-52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation. CONCLUSIONS: Neuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life.

Endoscopic ultrasound in solid pancreatic masses--current state and review of the literature.

Some 25 years ago endoscopic ultrasound (EUS) was introduced in clinical practice for better visualization of pancreas. At the time of introduction EUS was superior to other methods in detection of pancreatic masses allowing tissue diagnosis by later introduced EUS-guided fine needle aspiration (FNA). During the time EUS was improved, electronic probes replaced mechanical probes adding ability of color Doppler, power Doppler, contrast enhanced endosonography as well as EUS elastography analysis. Meanwhile, CT technology has also experienced significant improvements raising the question whether EUS has lost ground in diagnostics of solid pancreatic masses. The aim of this review was to discuss the current evidence of clinical impact of EUS and EUS-FNA in evaluation of solid pancreatic masses with special emphasis on differentiation between benign and malignant pancreatic lesions. According to the literature, the detection of small pancreatic tumors, preoperative localization of pancreatic endocrine tumors and tissue sampling by fine-needle aspiration of pancreatic masses in cases with therapeutic consequences are considered firm indications for EUS. Cytological tissue analysis remains undisputed in differentiation benign from malignant lesions, but the question when FNA is needed is discussed. Color Doppler, power Doppler, contrast enhanced endosonography and especially elastography are also discussed as tools that are bringing additional information in evaluation of pancreatic masses, however insufficient for definitive judgment of the lesion's nature. Pancreatic cancer staging as indication for EUS is discussed controversially, inconsistent results and conflicting evidence in literature making adequate conclusion impossible. However, this indicates that at least the role of EUS is no longer undisputed in this matter. Resuming the role of EUS we can state that despite some controversies EUS is very valuable method in evaluation of solid pancreatic masses and with EUS guided FNA is nowadays by far the best method for obtaining tissue diagnosis.

[Biochemical markers in assessment of severity and prognosis of acute pancreatitis]. / Biokemijski parametri u procjeni tezine i prognoze akutnog pankreatitisa.

The authors reveal and discuss the role of novel biochemical parameters in early diagnosis of acute pancreatitis and assessment of the severity of the disease. These biochemical parameters, beside routinely used amilase and lipase, might enable us to early identify those patients who are at risk of developing severe form of pancreatitis or complications. These parameters include trypsinogen activation peptide (TAP), C-reactive protein (CRP, tripsinogen-2, procalcitonin, phospholipase-A2 (PLA2), carboxypeptidase activation peptide (CAPAP) and interleukin-6 and 8 (IL-6, IL-8). Although these markers are still not incorporated in routine clinical practice, IL-6, IL-10, procalcitonin and trypsinogen activation peptide seem to have a good chance to be used as a new biochemical markers in assessment of severity and prognosis of acute pancreatitis.

[The role of endoscopic ultrasound in digestive tract diseases in era of advanced techniques of computed tomography]. / Uloga endoskopskog ultrazvuka u bolestima probavnog sustava u eri naprednih tehnika kompjutorizirane tomografije.

During the last 20 years endoscopic ultrasound (EUS) has been established as a highly accurate method in the diagnosis of digestive tract diseases. This method enables analysis of the lesions within the bowel wall, pancreas, and biliary system with utmost precision. Good results have also been achieved in evaluation of regional lymphadenopathy in staging of malignant diseases. Principal limitations of this method originate from its low accesibility and technical complexity which requires well trained sinologist and scientific evaluation of results in order to achieve adequate level of skill. Complications occur rarely with numbers comparable to other endoscopic procedures. With new software and hardware device introduced, computerized tomography (CT) (this refers in the first place to multidetector row CT) has been tremendously upgraded approaching the EUS in diagnostic accuracy in mentioned indications, and overcoming it in detection of distant metastases. Implementation of 3D reconstruction techniques allowed CT to enter the area of classic endoscopy, as in the case of virtual gastroscopy and/or colonoscopy. CT is a noninvasive method, very acceptable to majority of patients, and therefore popular and more prevalent compared to EUS. Although comparable in diagnostic accuracy in majority of indications, endosonography retains advance in evaluation of lesions within GI tract wall (including the early stages of carcinoma), detection of small biliary stones and small pancreatic tumors. Moreover, EUS is indespensable in therapeutic indications. Experiences with fine needle aspiration, punctions and drainage of cysts and abscesses, celiac plexus neurolysis and creation of digestive anastomosis confirm its place and value among the minimally invasive procedures which minimize the need for surgical intervention, patients' trauma and treatment costs.

[Doxycycline induced esophageal ulcers: report of two cases and review of the literature]. / Vrijedovi jednjaka prouzroceni doksiciklinom: prikaz dvaju bolesnika i pregled literature.

Doxycycline-induced esophageal ulcers (DIEU) are rarely observed in endoscopy units. On the other hand doxycycline itself has been claimed as an offending drug in 1/4 out of about 1000 cases of drug induced esophageal ulcers reported in the literature so far. In this article we present two patients with typical history and endoscopic features of esophageal ulcers as an consequence of doxycycline therapy. The therapy consisted of doxycycline withdrawal along with treatment with proton pump inhibitors and sucralfate which had led to disappearance of chest discomfort within one week period. Fourteen days of the tratment beginning complete recovery of the mucosal defects has occurred in both patients. In conclusion, in case of chest pain and painful swallowing occurring in a person who takes doxycycline, DIEU has to be considered followed by the esophagoscopy which would confirm clinical suspicious with high specificity leading to correct diagnosis and treatment of this condition.