Improved Nutritional Outcomes and Gastrointestinal Symptoms in Adult Cystic Fibrosis Patients Treated with Elexacaftor/Tezacaftor/Ivacaftor.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with cystic fibrosis (CF) on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. METHODS: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. RESULTS: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only 1 patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 µg/g to 442.1 µg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). CONCLUSION: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction.

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results: Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions: Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors.

16S rRNA gene primer choice impacts off-target amplification in human gastrointestinal tract biopsies and microbiome profiling.

16S rRNA amplicon sequencing or, more recently, metatranscriptomic analysis are currently the only preferred methods for microbial profiling of samples containing a predominant ratio of human to bacterial DNA. However, due to the off-target amplification of human DNA, current protocols are inadequate for bioptic samples. Here we present an efficient, reliable, and affordable method for the bacteriome analysis of clinical samples human DNA content predominates. We determined the microbiota profile in a total of 40 human biopsies of the esophagus, stomach, and duodenum using 16S rRNA amplicon sequencing with the widely used 515F-806R (V4) primers targeting the V4 region, 68F-338R primers and a modified set of 68F-338R (V1-V2M) primers targeting the V1-V2 region. With the V4 primers, on average 70% of amplicon sequence variants (ASV) mapped to the human genome. On the other hand, this off-target amplification was absent when using the V1-V2M primers. Moreover, the V1-V2M primers provided significantly higher taxonomic richness and reproducibility of analysis compared to the V4 primers. We conclude that the V1-V2M 16S rRNA sequencing method is reliable, cost-effective, and applicable for low-bacterial abundant human samples in medical research.

The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years' experience of association studies to understand the genetic architecture of pancreatic cancer.

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.

Management of pheochromocytomas and paragangliomas: Review of current diagnosis and treatment options.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022.

MR1: ESGE recommends small-bowel capsule endoscopy as the first-line examination, before consideration of other endoscopic and radiological diagnostic tests for suspected small-bowel bleeding, given the excellent safety profile of capsule endoscopy, its patient tolerability, and its potential to visualize the entire small-bowel mucosa.Strong recommendation, moderate quality evidence. MR2: ESGE recommends small-bowel capsule endoscopy in patients with overt suspected small-bowel bleeding as soon as possible after the bleeding episode, ideally within 48 hours, to maximize the diagnostic and subsequent therapeutic yield.Strong recommendation, high quality evidence. MR3: ESGE does not recommend routine second-look endoscopy prior to small-bowel capsule endoscopy in patients with suspected small-bowel bleeding or iron-deficiency anemia.Strong recommendation, low quality evidence. MR4: ESGE recommends conservative management in those patients with suspected small-bowel bleeding and high quality negative small-bowel capsule endoscopy.Strong recommendation, moderate quality evidence. MR5: ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by small-bowel capsule endoscopy.Strong recommendation, high quality evidence. MR6: ESGE recommends the performance of small-bowel capsule endoscopy as a first-line examination in patients with iron-deficiency anemia when small bowel evaluation is indicated.Strong recommendation, high quality evidence. MR7: ESGE recommends small-bowel capsule endoscopy in patients with suspected Crohn's disease and negative ileocolonoscopy findings as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known bowel stenosis.Strong recommendation, high quality evidence. MR8: ESGE recommends, in patients with unremarkable or nondiagnostic findings from dedicated small-bowel cross-sectional imaging, small-bowel capsule endoscopy as a subsequent investigation if deemed likely to influence patient management.Strong recommendation, low quality evidence. MR9: ESGE recommends, in patients with established Crohn's disease, the use of a patency capsule before small-bowel capsule endoscopy to decrease the capsule retention rate.Strong recommendation, moderate quality evidence. MR10: ESGE recommends device-assisted enteroscopy (DAE) as an alternative to surgery for foreign bodies retained in the small bowel requiring retrieval in patients without acute intestinal obstruction.Strong recommendation, moderate quality evidence. MR11: ESGE recommends DAE-endoscopic retrograde cholangiopancreatography (DAE-ERCP) as a first-line endoscopic approach to treat pancreaticobiliary diseases in patients with surgically altered anatomy (except for Billroth II patients).Strong recommendation, moderate quality evidence.

Current trends in the diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Currently, early detection is considered to be the most effective way to improve survival as radical resection is the only potential cure. PDAC is often divided into four categories based on the extent of disease: resectable, borderline resectable, locally advanced, and metastatic. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. This is mainly due to the lack of or vague symptoms while the disease is still localized, although appropriate utilization and prompt availability of adequate diagnostic tools is also critical given the aggressive nature of the disease. A cost-effective biomarker with high specificity and sensitivity allowing early detection of PDAC without the need for advanced or invasive methods is still not available. This leaves the diagnosis dependent on radiodiagnostic methods or endoscopic ultrasound. Here we summarize the latest epidemiological data, risk factors, clinical manifestation, and current diagnostic trends and implications of PDAC focusing on serum biomarkers and imaging modalities. Additionally, up-to-date management and therapeutic algorithms are outlined.

Lack of Association between Epidermal Growth Factor or Its Receptor and Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma: A Case-Control Study.

The epidermal growth factor (EGF) and its receptor (EGFR) gene-gene interactions were shown to increase the susceptibility to esophageal cancer. However, the role of the EGF/EGFR pathway in the development of gastroesophageal reflux disease (GERD) and its complications (reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC)) remains unclear. This association study is aimed at investigating functional EGF and EGFR gene polymorphisms, their mRNA expression in esophageal tissues, and EGF plasma levels in relation to RE, BE, and EAC development in the Central European population. 301 patients with RE/BE/EAC (cases) as well as 98 patients with nonerosive reflux disease (NERD) and 8 healthy individuals (controls) were genotyped for +61 A>G EGF (rs4444903) and +142285 G>A EGFR (rs2227983) polymorphisms using the TaqMan quantitative polymerase chain reaction (qPCR). In random subgroups, the EGF and EGFR mRNA expressions were analyzed by reverse transcription qPCR in esophageal tissue with and without endoscopically visible pathological changes; and the EGF plasma levels were determined by enzyme-linked immunosorbent assay. None of the genotyped SNPs nor EGF-EGFR genotype interactions were associated with RE, BE, or EAC development (p > 0.05). Moreover, mRNA expression of neither EGF nor EGFR differed between samples of the esophageal tissue with and without endoscopically visible pathology (p > 0.05) nor between samples from patients with different diagnoses, i.e., RE, BE, or EAC (p > 0.05). Nevertheless, the lower EGF mRNA expression in carriers of combined genotypes AA +61 EGF (rs4444903) and GG +142285 EGFR (rs2227983; p < 0.05) suggests a possible direct/indirect effect of EGF-EGFR gene interactions on EGF gene expression. In conclusion, EGF and EGFR gene variants and their mRNA/protein expression were not associated with RE, BE or EAC development in the Central European population.

Skin manifestations of pancreatic diseases.

Although symptoms of pancreatic diseases such as pancreatitis, acute and chronic and, carcinoma of the pancreas are mainly gastrointestinal in nature, the extra-pancreatic symptoms are also important. These include skin symptoms, such as pancreatic panniculitis, acanthosis nigricans, livedo reticularis, necrolytic migratory erythema, cutaneous signs of hemorrhage, as in persons with severe acute pancreatitis, or the finding of cutaneous metastases of pancreatic carcinoma, which may be a sign of advanced disease. The pancreas is therefore one of those organs for which diagnosis and therapy are often multidisciplinary. In this review article, we summarize current knowledge of the possible skin manifestations of pancreatic disorders.

The Use of Confocal Laser Endomicroscopy in Diagnosing Barrett's Esophagus and Esophageal Adenocarcinoma.

Confocal laser endomicroscopy (CLE) is a diagnostic technique that enables real-time microscopic imaging during microscopic examination and evaluation of epithelial structures with 1000-fold magnification. CLE can be used in the diagnosis of various pathologies, in pneumology, and in urology, and it is very widely utilized in gastroenterology, most importantly in the diagnosis of Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), biliary strictures, and cystic pancreatic lesions. A literature search was made in MEDLINE/PubMed and Google Scholar databases while focusing on diagnostics using CLE of BE and EAC. We then examined randomized and observational studies, systematic reviews, and meta-analyses relating to the utilization of CLE in BE and EAC diagnostics. Here, we discuss whether CLE can be a suitable diagnostic method for surveillance of BE. Even though many studies have proven that CLE increases diagnostic accuracy in detecting neoplastic transformation of BE, CLE is still not used as a standard diagnostic tool in BE surveillance due to a deficiency of scientific evidence. More studies and data are needed if CLE is to find a place as a new technique in BE surveillance.

Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study].

AIMS: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. METHODS: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients' demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. RESULTS: In all, 44 IBD patients were included, of whom 75% had Crohn's disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. CONCLUSIONS: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

Achalasia and acromegaly: Co-incidence of these diseases or a new syndrome?

BACKGROUND: Acromegaly is a disorder associated with hypersecretion of growth hormone, most usually caused by a pituitary adenoma. Dysmotility of the gastrointestinal tract has been reported in acromegalic patients. Achalasia is a disorder characterized by aperistalsis of the oesophagus with incomplete lower oesophageal sphincter relaxation and whose aetiology remains unknown. Mutations in some genes have previously been associated with the development of acromegaly or achalasia. The study aims were to analyse mutations in selected genes in a woman having both of these diseases, to identify their aetiological factors, and to suggest explanations for the co-incidence of acromegaly and achalasia. METHODS AND RESULTS: A female patient with acromegaly, achalasia, and a multinodular thyroid gland with hyperplastic colloid nodules underwent successful treatment of achalasia via laparoscopic Heller myotomy, a thyroidectomy was performed, and the pituitary macroadenoma was surgically excised via transnasal endoscopic extirpation. Germline DNA from the leukocytes was analysed by sequencing methods for a panel of genes. No pathogenic mutation in AAAS, AIP, MEN1, CDKN1B, PRKAR1A, SDHB, GPR101, and GNAS genes was found in germline DNA. The somatic mutation c.601C>T/p.R201C in the GNAS gene was identified in DNA extracted from a tissue sample of the pituitary macroadenoma. CONCLUSIONS: We here describe the first case report to our knowledge of a patient with both acromegaly and achalasia. Association of acromegaly and soft muscle tissue hypertrophy may contribute to achalasia's development. If one of these diagnoses is determined, the other also should be considered along with increased risk of oesophageal and colorectal malignancy.

Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis.

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.

The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient's blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.

Differentiating Primary Sclerosing Cholangitis from Similar Diseases of Autoimmune Origin.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease. Differential diagnostics can confuse it with immunoglobulin (Ig) G4-related sclerosing cholangitis (SC), an IgG4-related disease with clearly proven autoimmune origin. Differential diagnosis is made even more challenging because PSC with increased IgG4 levels (PSC-increased IgG4) also occurs. In order to facilitate their differential diagnosis, we reviewed recent literature regarding the etiologies, identifying characteristics, the most useful diagnostics, treatment, and the progression of these partially similar diseases. It is clear that PSC's pathogenesis differs from that of IgG4-related SC. In any differential diagnosis between PSC and PSC-increased IgG4, high IgG1 and low or normal IgG2 levels are characteristic for patients with PSC. Histological examination of the biliary tree wall in patients with IgG4-related SC typically reveals such changes as storiform fibrosis, obliterative phlebitis, and venulitis. These are absent in PSC-increased IgG4, which is characterized by a typical circular thickness in different parts of the biliary ducts. Finally, PSC is associated with inflammatory bowel disease, which is rare in IgG4-related SC, and more frequently is associated with cholangiocarcinomas and colon cancers. As distinct from IgG4-related SC, PSC is not a primary autoimmune disease.

Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis.

Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world's population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer's disease, demyelinating multiple sclerosis and Parkinson's disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.

The combination of endoluminal radiofrequency ablation and metal stent implantation for the treatment of malignant biliary stenosis - Randomized study.

PURPOSE: To analyse whether endobiliary radiofrequency ablation prior metal stent insertion in malignant biliary stenosis show improved survival or stent patency. METHODS: 76 patients with histologically proven malignant biliary stenosis have been enrolled in a prospective, randomized study. In control arm, 40 patients underwent self-expandable metal stent insertion. In experimental arm, the endoluminal ablation with a bipolar radiofrequency catheter was performed immediately before stent insertion. A subgroup analysis of cholangiocarcinoma was performed (22 vs 21 patients). The objective of the study was to determine the rate of complications, duration of the stent patency and the survival of patients (Kaplan-Meier analysis). RESULTS: No major complications related to the stent insertion and the endoluminal ablation were found. The mean primary stent patency was 5.2 (95% CI 0.7-12.8) vs 4.8 months (95% CI 0.8-18.2) months (p = 0.79) in control and experimental group, respectively, in the subgroup analysis with cholangiocarcinoma 4.5 (95% CI 0.8-10.3) and 9.6 (95% CI 5.2-11.2) months (p = 0.029). The median survival since the insertion of the stent was 6.8 (95 %CI 3.0-10.6) vs 5.2 (95 %CI 2.4-7.9) months (p = 0.495) and since the initial drainage 9.8 (95 %CI 6.9-12.7) vs 9.1 (95 %CI 5.4-12.7) months (p = 0.720) in the control and experimental arm. CONCLUSION: Endobiliary radiofrequency ablation prior metal stent insertion showed increased patency rate only in patients with cholangiocarcinoma, on the other hand, no improvement in survival was demonstrated in this randomized clinical study.