Role of advanced endoscopy in the management of inflammatory digestive diseases (pancreas and biliary tract).

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case.

[Endoscopic intraluminal treatment of early biliary complications after orthotopic liver transplantation]. / Opyt endoskopicheskogo vnutriprosvetnogo lecheniya rannikh biliarnykh oslozhnenii posle ortotopicheskoi transplantatsii pecheni.

OBJECTIVE: To improve the outcomes after orthotopic liver transplantation (OLT) followed by early biliary complications via endoscopic bilioduodenal stenting. MATERIAL AND METHODS: The study enrolled 41 patients with early biliary complications within 90 days after OLT. All patients underwent endoscopic treatment between 2001 and 2021. There were 34 (82.9%) men and 7 (17.1%) women aged 48.5±12.5 years. Strictures and failure of biliary anastomosis occurred in 33 (80.5%) and 8 (19.5%) patients, respectively. RESULTS: After endoscopic treatment, serum bilirubin normalized in 3.3±0.86 days in patients with strictures (23.7 (16.4; 34.5) mmol/l, p<0.001). Diameter of lobar ducts as a criterion of biliary hypertension was normalized after 4 (2.5; 5.5) days (p<0.001). Bile leakage after stenting with a covered self-expanding stent regressed in all 7 patients after 3 (2; 5) days. In 1 patient, bile output through the drainage stopped in 8 days after bilioduodenal stenting with a plastic stent. CONCLUSION: Endoscopic bilioduodenal stenting is always effective and minimally invasive treatment after liver transplantation followed by early biliary complications (failure or stricture of anastomosis). This approach minimizes postoperative complications (9.8%) that do not require surgical intervention (Clavien-Dindo grade I).

Artificial intelligence in pancreaticobiliary endoscopy.

Artificial intelligence (AI) applications in health care have exponentially increased in recent years, and a few of these are related to pancreatobiliary disorders. AI-based methods were applied to extract information, in prognostication, to guide clinical treatment decisions and in pancreatobiliary endoscopy to characterize lesions. AI applications in endoscopy are expected to reduce inter-operator variability, improve the accuracy of diagnosis, and assist in therapeutic decision-making in real time. AI-based literature must however be interpreted with caution given the limited external validation. A multidisciplinary approach combining clinical and imaging or endoscopy data will better utilize AI-based technologies to further improve patient care.

Applications of artificial intelligence in pancreatic and biliary diseases.

The application of artificial intelligence (AI) in medicine has increased rapidly with respect to tasks including disease detection/diagnosis, risk stratification, and prognosis prediction. With recent advances in computing power and algorithms, AI has shown promise in taking advantage of vast electronic health data and imaging studies to supplement clinicians. Machine learning and deep learning are the most widely used AI methodologies for medical research and have been applied in pancreatobiliary diseases for which diagnosis and treatment selection are often complicated and require joint consideration of data from multiple sources. The aim of this review is to provide a concise introduction of the major AI methodologies and the current landscape of AI research in pancreatobiliary diseases.

The Challenges of Implementing Artificial Intelligence into Surgical Practice.

BACKGROUND: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD). METHODS: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted. RESULTS: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones. CONCLUSION: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.

Incidence and Risk Factors of Gastrointestinal and Hepatobiliary Complications after Spinal Fusion Surgery: a Retrospective Cohort Study.

BACKGROUND: Spinal surgery holds a higher chance of unpredicted postoperative medical complications among orthopedic surgeries. Several studies have analyzed the risk factors for diverse postoperative medical complications, but the majority investigated incidences of each complication qualitatively. Among gastrointestinal complications, reports regarding postoperative ileus were relatively frequent. However, risk factors or incidences of hepatobiliary complications have yet to be investigated. The purpose of this study was to examine the incidence of gastrointestinal complications after spinal surgery, quantitatively analyze the risk factors of frequent complications, and to determine cues requiring early approaches. METHODS: In total, 234 consecutive patients who underwent spinal fusion surgery performed by one senior doctor at our institute in one-year period were retrospectively enrolled for analyses. The primary outcomes were presence of paralytic ileus, elevated serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and elevated total bilirubin levels. Univariate logistic regression analyses of all variables were performed. In turn, significant results were reanalyzed by multivariate logistic regression. The variables used were adjusted with age and gender. RESULTS: Gastrointestinal complications were observed in 15.8% of patients. Upon the risk factors of postoperative ileus, duration of anesthesia (odds ratio [OR], 1.373; P = 0.015), number of fused segments (OR, 1.202; P = 0.047), and hepatobiliary diseases (OR, 2.976; P = 0.029) were significantly different. For elevated liver enzymes, men (OR, 2.717; P = 0.003), number of fused segments (OR, 1.234; P = 0.033), and underlying hepatobiliary (OR, 2.704; P = 0.031) and rheumatoid diseases (OR, 5.021; P = 0.012) had significantly different results. Lastly, risk factors for total bilirubin elevation were: duration of anesthesia (OR, 1.431; P = 0.008), number of fused segments (OR, 1.359; P = 0.001), underlying hepatobiliary diseases (OR, 3.426; P = 0.014), and thoracolumbar junction involving fusions (OR, 4.134; P = 0.002) compared to lumbar spine limited fusions. CONCLUSION: Patients on postoperative care after spinal surgery should receive direct attention as soon as possible after manifesting abdominal symptoms. Laboratory and radiologic results must be carefully reviewed, and early consultation to gastroenterologists or general surgeons is recommended to avoid preventable complications.

GC-MS based metabolomics strategy to distinguish three types of acute pancreatitis.

Acute pancreatitis (AP) is a progressive systemic inflammatory response with high morbidity and high mortality, which is mainly caused by alcohol, bulimia, gallstones and hyperlipidemia. The early diagnosis of different types of AP and further explore potential pathophysiological mechanism of each type of AP is beneficial for optimized treatment strategies and better patient's care. In this study, a metabolomics approach based on gas chromatography-mass spectrometry (GC-MS), and random forests algorithm was established to distinguish biliary acute pancreatitis (BAP), Hyperlipidemia acute pancreatitis (HLAP), and alcoholic acute pancreatitis (AAP), from healthy controls. The classification accuracies for BAP, HLAP, and AAP patients compared with healthy control, were 0.886, 0.906 and 0.857, respectively, by using 5-fold cross-validation method. And some special metabolites for each type of AP were discovered, such as l-Lactic acid, (R)-3-Hydroxybutyric acid, Phosphoric acid, Glycine, Erythronic acid, l-Phenylalanine, d-Galactose, l-Tyrosine, Arachidonic acid, Glycerol 1-hexadecanoate. Furthermore, associations between these metabolites with the metabolism of amino acids, fatty acids were identified. Our studies have illuminated the biomarkers and physiological mechanism of disease in a clinical setting, which suggested that metabolomics is a valuable tool for identifying the molecular mechanisms that are involved in the etiology of BAP, AAP, HLAP and thus novel therapeutic targets.

Endoscopic management of biliary leaks: a systematic review with meta-analysis.

BACKGROUND: The first-line approach to the treatment of biliary leaks is endoscopic retrograde cholangiopancreatography. A variety of techniques can be used, including sphincterotomy, stenting, a combination of both techniques, or nasobiliary drainage. We performed a systematic review with meta-analysis to define the optimal strategy. METHODS: We searched MEDLINE/PubMed, EMBASE, CENTRAL, Scopus, Google Scholar, and Web of Science until January 2018 for randomized clinical trials, case-control studies, and prospective cohort studies. Data on procedure, success, and complication rate were extracted. Risk of bias was assessed. A network meta-analysis was performed to compare sphincterotomy alone vs. stenting alone vs. combination treatment. Stenting was further stratified into leak-bridging and short stenting. RESULTS: 11 studies out of 5085 references were included. Compared with sphincterotomy alone, the combination of sphincterotomy with leak-bridging stenting had the highest success rate (risk ratio [RR] 1.15, 95 % confidence interval [CI] 0.97 - 1.50), followed by leak-bridging stenting alone (RR 1.10, 95 %CI 0.84 - 1.44). For nonbridgeable leaks, stenting alone had a higher success rate than sphincterotomy alone (RR 1.07, 95 %CI 0.72 - 1.40). The combination of short stents with sphincterotomy had no added benefit (RR 0.94, 95 %CI 0.49 - 1.29). Overall quality of the included studies was considered to be moderate. CONCLUSIONS: We recommend sphincterotomy with stenting if the biliary leak can be bridged. If not, stenting alone with a short stent may be preferred in order to avoid sphincterotomy-related complications. More and larger studies are needed to confirm these findings.

Percutaneous Transjejunal Biliary Access in 60 Patients with Bilioenteric Anastomoses.

PURPOSE: To determine success and complication rates of percutaneous transjejunal biliary access (PTJBA) in patients with bilioenteric anastomoses. MATERIALS AND METHODS: In a single-center, retrospective study, 169 PTJBA procedures were performed over a 13.8-y period in 60 subjects (47 male; mean age, 54.5 y). Indications for biliary interventions were cholangitis (137 cases, 45 subjects) or hyperbilirubinemia (32 cases, 18 subjects). All patients had antecolic bilioenteric anastomoses without surgical fixation to the peritoneum (liver transplantation with hepaticojejunostomy, n = 37; hepatectomy with hepaticojejunostomy, n = 8; hepaticojejunostomy only, n = 12; pancreaticoduodenectomy, n = 3). RESULTS: Initial PTJBA was successful in 140 cases (82.8%) in 35 subjects (58.3%). Twenty-one additional PTJBAs (12.4%) in 18 subjects (30.0%) were performed secondarily following a conventional transhepatic approach. Radiographic markers on the Roux-en-Y limb (P = .14, odds ratio [OR] = 2.98) or preprocedural imaging (P = .13, OR = 10.00) did not increase the odds of successful PTJBA. There were 7 major complications (4.3%) in 6 patients (10.0%) requiring hospitalization longer than 5 d, and 37 minor complications (23.0%) in 19 patients (31.7%). No procedure-related mortality was observed. Minor and major complication rates were not affected by time between bilioenteric anastomosis creation and PTJBA (P = .70, OR = 1.00; P = .62, OR = 1.00), longer dwell time of a transjejunal drain (P = .68, OR = 1.02; P = .49, OR = 0.71), or access size (P = .40, OR = 0.85; P = .23, OR = 0.59). CONCLUSIONS: PTJBA is a relatively safe technique with a high success rate in patients with bilioenteric loops that are not surgically fixed to the peritoneum.

Hepatic hilar mass in an adolescent: a rare case of hepatobiliary tuberculosis.

BACKGROUND: Hepatobiliary tuberculosis is a rare manifestation of Mycobacterium tuberculosis infection, especially in younger patients. The non-specific symptoms and signs as well as the lack of definite imaging characteristics often impedes diagnosis. Definite diagnosis of tuberculosiscan be obtained through histopathological examination; conventional anti-tuberculosis drugs and surgery are the most commonly recommended treatments. CASE PRESENTATION: A previously healthy 15-year-old rural adolescent male presented with a 2-month history of weight loss and fatigue. We strongly suspected a Klatskin tumor; therefore, exploratory laparotomy was performed. However, the microscopical findings revealed a granuloma consisting of epithelioid cells, caseous necrosis, and lymphocytic infiltration, indicating caseating granulomatous inflammation and yielding a final diagnosis of hepatic hilar tuberculosis. CONCLUSION: Hepatic hilar tuberculosis is an extremely rare case; few physicians may have actually treated a case. This report therefore aims to improve the overall understanding of lymphatic tuberculosis of the hepatic hilum.

Prognosis of liver abscess with no identified organism.

BACKGROUND: There are limited studies focusing on liver abscess with negative microbiological cultures. This study evaluated the clinical and prognostic differences of patients with culture-negative liver abscess (CNLA) compared to those with a positive culture (CPLA) and compared these factors between K. pneumoniae liver abscess (KLA) and E. coli liver abscess (ELA). METHODS: A retrospective study of the patients who admitted with a liver abscess at two tertiary hospitals in Korea from 2012 to 2016 was performed. RESULTS: Among a total of 402 patients with liver abscess, 61.2% had positive cultures. K. pneumoniae (n = 133) was the most common cause, followed by E. coli (n = 74). Patients with CPLA were significantly older (p = 0.02) and more frequently had cholelithiasis or biliary tract disease (p = 0.001) compared to patients with CNLA. In-hospital mortality (p = 0.63) and recurrence (p = 0.77) were no different between the two groups. The length of hospital stay was significantly longer in patients with CPLA (p = 0.03) compared with those with CNLA. Subgroup analysis for patients who received 3rd generation cephalosporins empirically showed that in-hospital mortality (p = 0.18) and recurrence (p = 0.27) were not also significantly different. Cholelithiasis, or biliary tract disease (p = 0.001), liver disease (p = 0.001), malignancy (p = 0.0001), and ESBL production (p = 0.0001) were found more frequently in patients with ELA compared with those with KLA. CONCLUSIONS: The prognosis of the CNLA patients was similar to that of the CPLA patients, although the length of hospital stay was shorter in the CNLA patients. The epidemiologic and clinical characteristics of the ELA patients are somewhat different than those of the KLA patients.

The interobserver agreement of optical features used to differentiate benign from neoplastic biliary lesions assessed at balloon-assisted cholangioscopy.

BACKGROUND AND AIM: Balloon-assisted cholangioscopy allows mucosal assessment of the biliary tree with pediatric endoscopes. No validated optical criteria exist to differentiate benign from neoplastic biliary lesions. We aimed to identify, validate, and revalidate optical features differentiating benign from neoplastic biliary lesions. Furthermore, we aimed to determine whether cholangioscopic appearance allows endoscopists to accurately differentiate benign from neoplastic biliary lesions. METHODS: Baseline: from 44 de-identified balloon-assisted cholangioscopy videos, a blinded investigator analyzed potential optical features distinguishing benign from neoplastic biliary lesions. VALIDATION: during the initial "teaching phase," 20 endoscopists viewed video clips of 11 optical features identified in the baseline study. At the subsequent "test phase," 20 further video clips were assessed by the endoscopists blinded to clinical details and questionnaires completed for the presence or absence of optical features, favored diagnosis and diagnostic confidence. Revalidation: The six identified optical features from the validation study with at least moderate agreement were revalidated the same way 12 months later assessing 20 new lesions. RESULTS: Baseline: 11 optical features were found to differentiate benign from neoplastic biliary lesions. Validation and revalidation: six optical features demonstrated at least moderate interobserver agreement (irregular margin, dark mucosa, adherent mucous, papillary projections, tubular, or branched/disorganized surface structures). Endoscopists correctly diagnosed lesions as benign in 89% and neoplastic in 83%. When highly confident, endoscopists correctly diagnosed 96% of benign and 87% neoplastic lesions. CONCLUSIONS: Six features were validated and revalidated to differentiate benign from neoplastic biliary lesions. When highly confident with a diagnosis, endoscopists usually differentiate benign from neoplastic biliary lesions.

Biliary leakage following pancreaticoduodenectomy: Prevalence, risk factors and management.

BACKGROUND: Few studies investigated biliary leakage after pancreaticoduodenectomy (PD) especially when compared to postoperative pancreatic fistula (POPF). This study was to determine the incidence of biliary leakage after PD, predisposing factors of biliary leakage, and its management. METHODS: We retrospectively studied all patients who underwent PD from January 2008 to December 2017 at Gastrointestinal Surgery Center, Mansoura University, Egypt. According to occurrence of postoperative biliary leakage, patients were divided into two groups. Group (1) included patients who developed biliary leakage and group (2) included patients without identified biliary leakage. The preoperative data, operative details, and postoperative morbidity and mortality were analyzed. RESULTS: The study included 555 patients. Forty-four patients (7.9%) developed biliary leakage. Ten patients (1.8%) had concomitant POPF. Multivariate analysis identified obesity and time needed for hepaticojejunostomy reconstruction as independent risk factors of biliary leakage, and no history of preoperative endoscopic retrograde cholangiopancreatiography (ERCP) as protective factor. Biliary leakage from hepaticojejunostomy after PD leads to a significant increase in development of delayed gastric emptying, and wound infection. The median hospital stay and time to resume oral intake were significantly greater in the biliary leakage group. Non-surgical management was needed in 40 patients (90.9%). Only 4 patients (9.1%) required re-exploration due to biliary peritonitis and associated POPF. The mortality rate in the biliary leakage group was significantly higher than that of the non-biliary leakage group (6.8% vs 3.9%, P = 0.05). CONCLUSIONS: Obesity and time needed for hepaticojejunostomy reconstruction are independent risk factors of biliary leakage, and no history of preoperative ERCP is protective factor. Biliary leakage increases the risk of morbidity and mortality especially if concomitant with POPF. However, biliary leakage can be conservatively managed in majority of cases.

Cell Interactions in Biliary Diseases: Clues from Pathophysiology and Repair Mechanisms to Foster Early Assessment.

In modern hepatology, diseases of the biliary epithelium, currently termed cholangiopathies, represent one of the main gaps in knowledge, both on experimental and clinical grounds, though they started to draw attention since the late 80s [...].

The role of bile leak testing in liver resection: a systematic review and meta-analysis.

BACKGROUND: Bile leak following liver resection can be associated with significant morbidity. This systematic review and meta-analysis aims to evaluate the effect of intraoperative bile leak testing on postoperative bile leak rate and other complications after liver resection without biliary reconstruction for any cause. METHODS: PubMed, MEDLINE, Embase, Cochrane Library and grey literature databases were searched for articles between 1960 and 2017 comparing bile leak rates with or without bile leak testing. Standard meta-analysis methods were used. The primary outcome was bile leak rate, and secondary outcomes were overall morbidity, reintervention rate and length of stay. RESULTS: 8 articles met inclusion criteria. Intraoperative bile leak testing after resection was associated with lower postoperative bile leak rate (4.1% vs 12.3%, OR 0.36, 95% CI 0.23-0.55, p < 0.001), overall morbidity (OR 0.67, 95% CI 0.47-0.96, p = 0.030), need for reintervention (OR 0.11, 95% CI 0.03-0.36, p < 0.001) and a shorter duration of hospital stay (2.21 days, 95% CI 0.69-3.73, p = 0.004). CONCLUSION: The routine use of intraoperative bile leak testing during liver resection results in a significant reduction in postoperative bile leak rate, overall morbidity, length of hospital stay and need for re-intervention. Bile leak testing should be performed after liver resection without biliary reconstruction.

Risk score to predict biliary leakage after elective liver resection.

BACKGROUND: Biliary leakage remains a major cause of morbidity after liver resection. Previous prognostic studies of posthepatectomy biliary leakage (PHBL) lacked power, population homogeneity, and model validation. The present study aimed to develop a risk score for predicting severe PHBL. METHODS: In this multicentre observational study, patients who underwent liver resection without hepaticojejunostomy in one of nine tertiary centres between 2012 and 2015 were randomly assigned to a development or validation cohort in a 2 : 1 ratio. A model predicting severe PHBL (International Study Group of Liver Surgery grade B/C) was developed and further validated. RESULTS: A total of 2218 procedures were included. PHBL of any severity and severe PHBL occurred in 141 (6·4 per cent) and 92 (4·1 per cent) patients respectively. In the development cohort (1475 patients), multivariable analysis identified blood loss of at least 500 ml, liver remnant ischaemia time 45 min or more, anatomical resection including segment VIII, transection along the right aspect of the left intersectional plane, and associating liver partition and portal vein ligation for staged hepatectomy as predictors of severe PHBL. A risk score (ranging from 0 to 5) was built using the development cohort (area under the receiver operating characteristic curve (AUROC) 0·79, 95 per cent c.i. 0·74 to 0·85) and tested successfully in the validation cohort (AUROC 0·70, 0·60 to 0·80). A score of at least 3 predicted an increase in severe PHBL (19·4 versus 2·6 per cent in the development cohort, P < 0·001; 15 versus 3·1 per cent in the validation cohort, P < 0·001). CONCLUSION: The present risk score reliably predicts severe PHBL. It represents a multi-institutionally validated prognostic tool that can be used to identify a subset of patients at high risk of severe PHBL after elective hepatectomy.

Possible involvement of interleukin-18 in the pathology of hepatobiliary adverse effects related to treatment with ceritinib.

BACKGROUND: Ceritinib demonstrated a statistically significant effect on the progression-free survival versus chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) as the first therapy or after previous treatment with crizotinib and one or two prior chemotherapy regimens in global phase 3 studies. However, some serious adverse effects related to ceritinib therapy were reported across these clinical studies. Among them, a grade 3 and 4 increase in hepatobiliary enzymes was one of the common adverse events related to treatment with ceritinib. However, the pathology remains unclear. Previously, increased Interleukin (IL)-18 was observed in both biliary duct disease and liver disease. Therefore, we hypothesized that IL-18 is involved in the pathology of hepatobiliary adverse effects related to treatment with ceritinib and evaluated the serum IL-18. CASE PRESENTATION: The patient was a 53-year-old Japanese woman that we previously reported as having severe hepatobiliary adverse effects related to ceritinib therapy. Laboratory data, CT and MRI were obtained at each time point. IL-18 was evaluated by ELISA method at each time point. Immunochemical staining of liver tissue was performed as a standard protocol using antibodies against IL-18. Our records showed that the levels of serum IL-18 increased from the early stage of hepatobiliary adverse effects related to the treatment with ceritinib and were became worse with an increase in hepatobiliary enzymes and the progression of imaging abnormalities in the bile duct. Furthermore, IL-18 positive cells were detected in the inflammatory sites around the interlobular bile duct of the liver tissue. CONCLUSION: Our case report shows that the increase of serum IL-18 had a positive correlation with the progression of severe hepatobiliary adverse effects related to treatment with ceritinib and the involvement of IL-18 in the hepatobiliary inflammation by pathological evaluation. These results suggest that IL-18 could be a useful surrogate marker for the hepatobiliary toxicity of ceritinib. However, this is only one case report and further prospective observations will complement our data in the future.

Current role of endoscopic cholangioscopy.

PURPOSE OF REVIEW: Every year more than one million people worldwide undergo an endoscopic retrograde cholangiopancreatography (ERCP) for disorders of the bile duct system. This review aims to discuss recent clinical data with regard to single-operator peroral cholangioscopy (POC). RECENT FINDINGS: Innovations and technical optimizations of POC devices have extended diagnostic and therapeutic options for patients with complex biliary disease. Most of the currently available clinically relevant data are obtained with the single-operator peroral cholangioscopy (SOC)-system SpyGlass, which in a period of a decade has evolved further to a digital platform with increasing applicability, usefulness and cost-effectiveness. SUMMARY: POC allows endoscopists to treat patients with complicated diseases of the gallbladder, liver, biliary tract, and pancreas better. In recent years, this technique was optimized to overcome prior limitations. The implementation of the single-operator SpyGlass Digital System in daily practice becomes a reality. We make an overview of the history of cholangioscopy, the technical evolution, and usefulness of this platform and take a look at its economic impact.