Search Results (18)

Background: Immune-mediated liver and biliary conditions, such as IgG4-related pancreatobiliary disease (IgG4-PB) and a subset of primary sclerosing cholangitis (PSC- high(h)IgG4), exhibit increased IgG4 levels in the blood. The relative expression of IgG4+ and IgG1+ B cells in the blood and the expression of complement and Fc receptors on these IgG1+ and IgG4+ B cells in IgG4-PB and PSC have not been previously described. We hypothesised that the patterns of expression of these cells and their receptors would differ, are relevant to disease pathogenesis and may represent therapeutic targets. Methods: CD19+ B cells were sorted from blood collected from patients with IgG4-PB, PSC-high(h)IgG4 and healthy volunteers. Cells were stained with fluorescent labelled antibodies specific to IgG1, IgG4, complement receptors (CR1 and CR2), Fc receptors (FcεRII and FcγRIIb) and chemokine receptors (CXCR3, CXCR4, CXCR5) and were analysed by flow cytometry. Findings: IgG4-PB, compared to healthy volunteers, showed decreased CR2 expression on IgG1+ B cells (MFI 416 (275–552) vs. 865 (515–3631), p = 0.04) and IgG4+ B cells (MFI 337 (231–353) vs. 571 (398–2521), p = 0.03). IgG4-PB, compared to healthy volunteers, showed increased FcεRII expression on IgG4+ B cells (MFI 296 (225–617) vs. 100 (92–138), p = 0.0145) and decreased FcγRIIb expression on IgG1+ B cells (134 (72–161) vs. 234 (175–291), p = 0.0262). FcγRIIb expression was also decreased in IgG1+ B cells in patients with PSC-hIgG4 compared to healthy volunteers. Conclusions: This exploratory study indicates that in IgG4-PB, B cells have decreased CR2 and FcγRIIb expression and increased FcεRII expression, suggesting altered sensitivity to complement, IgG-mediated inhibition and sensitisation by IgE, which may promote the relative expansion of IgG4+ B cells in this disease. Full article

Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35–6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94–16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56–6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments. Full article

Background/Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated disorder presenting as mass-like lesions with obstructions. An elevated serum IgG4 level is identified in more than half of affected patients and is considered a diagnostic criterion. IgG4-RD is still easily misdiagnosed as neoplastic or infectious disease. We aimed to conduct a hospital-based study to illuminate the association between serum IgG4 levels and pancreatobiliary disorders and cancer. Methods: In this study, serum IgG4 levels were assessed at our hospital’s immunology laboratory, utilizing data from the hospital’s computer center, and the diagnostic codes used were based on ICD-9-CM. We analyzed IgG4 level data collected between April 2013 and April 2020, including patients’ age, gender, and diseases, but excluding the rationale for IgG4 level assessment. Employing propensity score matching (PSM) at a 1:1 ratio to mitigate age and gender confounding, we analyzed 759 patients divided into groups by IgG4 levels (≤140 and >140 mg/dL; and ≤140, 141–280, >280 mg/dL). We explored associations between IgG4 levels and conditions such as pancreatobiliary cancer (the group included cholangiocarcinoma, pancreatic cancer, and ampullary cancer), cholangitis, cholangiocarcinoma, pancreatitis, pancreatic cancer, and ampullary cancer. Results: Our study analyzed the demographics, characteristics, and serum IgG4 levels of participants and found no significant differences in serum IgG4 levels across various pancreatobiliary conditions. Nevertheless, the crude odds ratios (ORs) suggested a nuanced association between a higher IgG4 level > 280 mg/dL and increased risks of cancer and pancreatitis, with crude ORs of 1.52 (p = 0.03) and 1.49 (p = 0.008), respectively. After PSM matching, the further analysis of 759 matched patients showed no significant differences in IgG4 levels > 140 mg/dL between cancerous and non-cancerous groups, nor across other pancreatobiliary conditions. A higher serum IgG4 level > 280 mg/dL was significantly associated with pancreatobiliary cancer and cholangiocarcinoma, with crude ORs of 1.61 (p = 0.026) and 1.62 (p = 0.044), respectively. In addition, IgG4 > 280 mg/dL showed a greater association with pancreatic cancer compared with 141–280 mg/dL, with crude OR of 2.18 (p = 0.038). Conclusions: Our study did not find a clear association between serum IgG4 levels (>140 mg/dL) and pancreatobiliary cancer. We observed that higher IgG4 levels (>280 mg/dL) may be associated with cholangiocarcinoma and pancreatic cancer, as indicated by crude ORs. However, the adjusted analysis did not demonstrate the significant association between IgG4 level > 280 mg/dL and cancer. Considering IgG4-RD as a chronic and persistent inflammatory status, it is more closely associated with inflammatory diseases than with cancer. Therefore, further long-term cohort studies are necessary to evaluate the potential role of IgG4 levels in cancer risk among these patients. Full article

Diabetes mellitus (DM) is a prominent risk factor for malignant and non-malignant pancreatic diseases. Furthermore, the presence of DM predicts an unfavourable outcome in people with pancreatic cancer. This retrospective observational study investigated 370 patients who underwent pancreatic resection surgery for various indications (84.3% in malignant indication) in a single surgery centre in Graz, Austria. The preoperative and postoperative diabetes statuses were evaluated according to surgery method and disease entity and predictors for diabetes development after surgery, as well as outcomes (survival and cancer recurrence) according to diabetes status, were analysed. In the entire cohort, the postoperative diabetes (postopDM) incidence was 29%. PostopDM occurred significantly more frequently in malignoma patients than in those with benign diseases (31.3% vs. 16.7%; p = 0.040, OR = 2.28). In the malignoma population, BMI, longer surgery duration, and prolonged ICU and hospital stay were significant predictors of diabetes development. The 1- and 2-year follow-ups showed a significantly increased mortality of people with postopDM in comparison to people without diabetes (HR 1-year = 2.02, p = 0.014 and HR 2-years = 1.56, p = 0.034). Local cancer recurrence was not influenced by the diabetes status. Postoperative new-onset diabetes seems to be associated with higher mortality of patients with pancreatic malignoma undergoing pancreatobiliary surgery. Full article

The peritoneum is a common site of metastases for gastrointestinal tumors that predicts a poor outcome. In addition to decreased survival, peritoneal metastases (PMs) can significantly impact quality of life from the resulting ascites and bowel obstructions. The peritoneum has been a target for regional therapies due to the unique properties of the blood–peritoneum barrier. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have become accepted treatments for limited-volume peritoneal disease in appendiceal, ovarian, and colorectal malignancies, but there are limitations. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) improves drug distribution and tissue penetration, allowing for a minimally invasive application for patients who are not CRS/HIPEC candidates based on high disease burden. PIPAC is an emerging treatment that may convert the patient to resectable disease, and may increase survival without major morbidity, as indicated by many small studies. In this review, we discuss the rationale and benefits of PIPAC, as well as sentinel papers describing its application for gastric, colorectal, appendiceal, and pancreatobiliary PMs. While no PIPAC device has yet met FDA approval, we discuss next steps needed to incorporate PIPAC into neoadjuvant/adjuvant treatment paradigms, as well as palliative settings. Data on active clinical trials using PIPAC are provided. Full article

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology. Full article

Immunoglobulin G4-related disease (IgG4-RD) is a fibrous inflammatory process related to immunomodulation. The involvement of the pancreato-biliary tract, retroperitoneum/aorta, head and neck, and salivary glands are the most frequently observed disease phenotypes, differing in their epidemiological features, serological findings, and prognostic outcomes. IgG4-RD was combined with oesophageal ulcers, and the patients were infected with cytomegalovirus at the time of the examination. This constituted a huge challenge in the diagnosis and treatment of oesophageal ulcers. We report the case of a 53-year-old male who experienced nausea, vomiting, and anaemia recurrently for many years. According to his medical records, an upper gastrointestinal endoscopy revealed an oesophageal ulcer, and he had had numerous hospital visits for anaemia but with no definitive diagnosis, and he had responded poorly to therapy. However, with persistent symptoms, he came to our hospital and, according to the results of the upper gastrointestinal endoscopy, a serum IgG4 test, and histopathological and immunohistochemical staining, he was finally diagnosed with IgG4-related oesophageal disease combined with a cytomegalovirus infection. We hope that through this case, we can learn more about IgG4-RD and, at the same time, give clinicians a better understanding of IgG4-RD combined with oesophageal ulceration, a new understanding of cytomegalovirus infections, and improved clinical knowledge. Full article

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an essential endoscopic tissue sampling method for diagnosing pancreatobiliary diseases; however, determining the presence of target specimens mixed in the blood by conventional observation is challenging due to the small size of the obtained sample. This study investigated the usefulness of a target sample check illuminator (TSCI) that emits a specific wavelength of light to determine the presence of target specimens. Twenty-seven patients who underwent EUS-FNA at our hospital were included. Conventional white light observation was performed for the collected samples, followed by TSCI; six people evaluated the presence of the target specimen on a 5-point scale. The target specimen discrimination score using TSCI (median: 5) was significantly higher than that using conventional white light observation (median: 1) (p < 0.001). No significant difference was observed in the discrimination score between the evaluator (novice vs. expert, p = 0.162) and puncture needle (22G vs. 25G, p = 0.196). The discriminability of TSCI in the samples obtained using EUS-FNA was significantly higher than that of conventional observation. TSCI does not depend on the evaluator or puncture needle for the identification of the target specimen; hence, it can provide a good pathological specimen and may contribute to the improvement of the diagnostic ability. Full article

Background and aim: Pancreato-biliary patients who undergo endoscopic procedures have high potential risk of delirium. Although benzodiazepine has traditionally been used to treat insomnia, this drug might increase delirium. Lemborexant may be useful for patients with insomnia, without worsening delirium, although there is no evidence for high-risk patients with pancreato-biliary disease. The aim of this pilot study was to evaluate the safety and efficacy of lemborexant for insomnia and the frequency of delirium after endoscopic procedures under deep sedation in patients with pancreato-biliary disease. Method: This retrospective study included consecutive patients who were administered lemborexant after endoscopic procedures for pancreato-biliary disease between September 2020 and June 2022. The primary outcome of this study was evaluation of the safety and efficacy of lemborexant for insomnia. Frequency of delirium was the secondary outcome. Result: In total, 64 patients who had the complication of insomnia after an endoscopic procedure were included in the study. Risk factors for delirium were advanced age (n = 36, 56.3%), dementia (n = 10, 15.6%), and regular alcohol use (n = 13, 20.3%), as well as the sedatives midazolam and pentazocine that were administered to all patients at the time of the endoscopic procedure. Successful asleep was achieved by 61/64 patients (95.3%). No fall event was observed during the night following the procedure in any patient. However, mild consciousness transformation was observed in one patient. Conclusions: In conclusion, lemborexant use may be effective and safe for use after endoscopic procedures in pancreato-biliary patients, without increasing the risk of delirium. Full article

Pancreatic cancer and cholangiocarcinoma are lethal diseases mainly diagnosed at an inoperable stage. As pancreatobiliary surgical specimens are often unavailable for further molecular testing, this review aimed to highlight the diagnostic, prognostic, and therapeutic impact of next-generation sequencing (NGS) performed on distinct small biopsies, including endoscopic ultrasound fine-needle aspirations and biopsies of pancreatic solid and cystic lesions, biliary duct brushings, and also “liquid biopsies” such as the pancreatic juice, bile, and blood. NGS could clarify indeterminate pancreatic lesions or biliary strictures, for instance by identifying TP53 or SMAD4 mutations indicating high-grade dysplasia or cancer. It could also stratify pancreatic cystic lesions, by distinguishing mucinous from non-mucinous cysts and identifying high-risk cysts that should be excised in surgically fit patients, whereas the combination of cytology, elevated cystic CEA levels and NGS could improve the overall diagnostic accuracy. When NGS is performed on the pancreatic juice, it could stratify high-risk patients under surveillance. On the plasma, it could dynamically monitor the disease course and response to therapy. Notably, the circulating tumor DNA (ctDNA) levels have been associated with staging, grading, and survival. Lastly, NGS has shown potential in identifying potentially actionable molecular alterations. In conclusion, NGS applied on small biopsies could carry significant diagnostic, prognostic, and therapeutic value. Full article

As the burden of liver disease in the general populace steadily increases, so does the need for both advanced diagnostic and treatment options. Endoscopic ultrasound is a reliable diagnostic and therapeutic method that has an established role, foremost in pancreatobiliary pathology. This paper aims to summarize the growing role of endoscopic ultrasound in hepatology based on the search of the current literature. A number of applications of endoscopic ultrasound are reviewed, including both noninvasive methods and tissue acquisition in focal and diffuse liver disease, portal hypertension measurement, detection and management of gastric and esophageal varices, treatment of focal liver lesions and staging of pancreatobiliary malignancies, treatment of cystic and solid liver lesions, as well as liver abscess drainage. Both hepatologists and endoscopists should be aware of the evolving role of endoscopic ultrasound in liver disease. The inherent invasive nature of endoscopic examination limits its use to a targeted population identified using noninvasive methods. Endoscopic ultrasound is one the most versatile methods in gastroenterology, allowing immediate access with detection, sampling, and treatment of digestive tract pathology. Further expansion of its use in hepatology is immanent. Full article

Detective flow imaging endoscopic ultrasonography (DFI-EUS) provides a new method to image and detect fine vessels and low-velocity blood flow without using ultrasound contrast agents. The aim of this study was to evaluate the utility of DFI-EUS for pancreatobiliary lesions and lymph nodes. Between January 2019 and January 2020, 53 patients who underwent DFI-EUS, e-FLOW EUS, and contrast-enhanced EUS were enrolled. The ability of DFI-EUS and e-FLOW EUS to detect vessels was compared with that of contrast-enhanced EUS. This article describes the DFI technique along with our first experience of its use for vascular assessment of pancreatobiliary lesions. Vessels were imaged in 34 pancreatic solid lesions, eight intraductal papillary mucinous neoplasms (IPMNs), seven gall bladder lesions, and four swollen lymph nodes. DFI-EUS (91%) was significantly superior to e-FLOW EUS (53%) with respect to detection of vessels (p < 0.001) and for discrimination of mural nodules from mucous clots in IPMN and gallbladder lesions from sludge (p = 0.046). Thus, DFI-EUS has the potential to become an essential tool for diagnosis and vascular assessment of various diseases. Full article

Over the last decades, contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) has emerged as an important diagnostic tool for the diagnosis and differentiation of several gastrointestinal diseases. The key advantage of CH-EUS is that the influx and washout of contrast in the target lesion can be observed in real time, accurately depicting microvasculature. CH-EUS is established as an evidence-based technique complementary to B-mode EUS to differentiate solid appearing structures, to characterize mass lesions, and to improve the staging of gastrointestinal and pancreatobiliary cancer. In the last few years, interest has increased in the use of CH-EUS in interventional procedures such as tissue acquisition, tumor ablation, biliary drainage, and the management of pancreatic fluid collections. The aim of this narrative review is to evaluate the available evidence and future expectations of CH-EUS in interventional EUS. Full article

Balloon enteroscopy-assisted endoscopic retrograde cholangiography (BEA-ERC) is useful and feasible in adults with pancreatobiliary diseases, but its efficacy and safety have not been established in pediatric patients. We compared the success rate and safety of BEA-ERC between adults and pediatric patients. This single-center retrospective study reviewed 348 patients (pediatric: 57, adult: 291) with surgically altered gastrointestinal anatomies who underwent BEA-ERC for biliary disorders from January 2007 to December 2019. The success rate of reaching the anastomosis or duodenal papilla was significantly lower in pediatric patients than in adult patients (66.7% vs. 88.0%, p < 0.01). The clinical success rate was also significantly lower in pediatric patients (64.9% vs. 80.4%, p = 0.014). The rate of adverse events was significantly higher in pediatric patients than in adults (14.2% vs. 7.7%, p = 0.037). However, if the anastomotic sites were reached in pediatric patients, the treatment was highly successful (97.3%). The time of reaching target site was significantly longer in pediatric patients than in adult patients. This study shows that BEA-ERC in pediatric patients is more difficult than that in adult patients. However, in patients where the balloon enteroscope was advanced to the anastomosis, clinical outcomes comparable to those in adults can be achieved. Full article